Lipid Profile, Serum Ceratinine, eGFR, Uric acid, Electrolytes, FBS, RBS, CBG, 2 Hours post glucose BS HBAIC Urinalysis Flashcards
is the most widely used marker for GFR, which is related directly to urine creatinine (UCr) excretion and inversely to PCr.
Plasma creatinine (PCr)
Urea clearance may underestimate GFR significantly
because of urea reabsorption by the tubule. In contrast, creatinine isderived from muscle metabolism of creatine, and its generation varies little from day to day
Creatinine clearance (CrCl), an approximation of GFR, is measured
from plasma and urinary creatinine excretion rates for a
defined period (usually 24 h) and is expressed in milliliters per
minute: CrCl = (Uvol × UCr)/(PCr × Tmin).
Creatinine is useful for
estimating GFR because it is a small, freely filtered solute that is
not reabsorbed by the tubules.
PCr levels can increase acutely from dietary ingestion of cooked meat, however, and creatinine can be
secreted into the proximal tubule through an organic cation pathway (especially in advanced progressive chronic kidney disease), leading
to overestimation of GFR.
Cockcroft-Gault:
CrCl (mL/min) =
140 − age (years) × weight (kg) × [0.85 if female]
/(72 × PCr (mg/dL).
a member of the cystatin superfamily of
cysteine protease inhibitors, is produced at a relatively constant rate from all nucleated cells. Serum cystatin C has been proposed to be a more sensitive marker of early GFR decline than is PCr; however, like
serum creatinine, cystatin C is influenced by the patient’s age, race,
and sex and also is associated with diabetes, smoking, and markers of
inflammation.
Cystatin C,
Patients with advanced chronic renal insufficiency often have some
proteinuria, nonconcentrated urine (isosthenuria; isosmotic with plasma), and small kidneys on ultrasound, characterized by increased echogenicity
and cortical thinning.
Decreased renal perfusion accounts for %
40–80% of cases of acute
renal failure and, if appropriately treated, is readily reversible. The etiologies of prerenal azotemia include any cause of decreased circulating blood volume (gastrointestinal hemorrhage, burns, diarrhea, diuretics), volume sequestration (pancreatitis, peritonitis,
rhabdomyolysis), or decreased effective arterial volume (cardiogenic shock, sepsis).
True or “effective” arterial hypovolemia leads to a fall in
mean arterial pressure, which in turn triggers a series of neural and humoral responses,
including activation of the sympathetic nervous
and renin-angiotensin-aldosterone systems and antidiuretic hormone (ADH) release.
GFR is maintained by prostaglandin-mediated relaxation of afferent arterioles and angiotensin II–mediated constriction
of efferent arterioles
Blockade of prostaglandin production by NSAIDs can result in severe vasoconstriction and acute renal failure
Blocking angiotensin action with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) decreases efferent arteriolar
tone and in turn decreases glomerular capillary perfusion pressure
Once the mean arterial pressure falls below ____
80 mmHg, GFR declines steeply
Patients with bilateral renal artery stenosis (or stenosis in a solitary kidney) are dependent on
efferent arteriolar vasoconstriction for maintenance of glomerular filtration pressure and are particularly susceptible to a precipitous decline in GFR when given ACE inhibitors or ARBs.
In prerenal conditions, the tubules are intact, leading to
a concentrated urine (>500 mosmol), avid Na retention (urine Na concentration, <20 mmol/L; fractional excretion of Na, <1%), and UCr/PCr >40
The prerenal urine sediment is usually normal or has hyaline and granular casts, whereas the sediment of ATN is
ATN usually is filled with cellular debris, tubular epithelial casts, and dark (muddy brown) granular casts
Laborat ory Findings in Acute Renal Failure
Prerenal Azotemia
BUN/PCr ratio >20:1 Urine sodium U Na, meq/L <20 Urine osmolality, mosmol/L H2O >500 Fractional excretion of sodiuma <1% Urine/plasma creatinine UCr/PCr >40 Urinalysis (casts) None or hyaline/ granular
Oliguric Acute Renal Failure BUN/PCr ratio 10–15:1 Urine sodium U Na, meq/L >40 Urine osmolality, mosmol/L H2O <350 Fractional excretion of sodiuma >2% Urine/plasma creatinine UCr/PCr <20 Urinalysis (casts) Muddy brown
Ischemic and toxic ATN account for %
~90% of cases of acute intrinsic renal failure
Ischemic ATN is observed most frequently in patients who have undergone major surgery, trauma, severe hypovolemia, overwhelming sepsis, or extensive burns.
Nephrotoxic ATN complicates the administration
of many common medications, usually by inducing a combination of intrarenal vasoconstriction, direct tubule toxicity, and/ or tubule obstruction. The kidney is vulnerable to toxic injury by virtue of its rich blood supply (25% of cardiac output) and its ability to concentrate and metabolize toxins. A diligent search for hypotension and nephrotoxins usually uncovers the specific etiology of ATN.
Urinalysis usually shows mild to moderate proteinuria, hematuria, and pyuria (~75% of cases) and occasionally WBC casts. The finding of RBC casts in interstitial nephritis has been reported but should prompt a search for glomerular diseases
Atheroembolic renal failure can occur spontaneously but most often is associated
with recent aortic instrumentation. The emboli are cholesterol-rich and lodge in medium and small renal arteries, with a consequent
eosinophil-rich inflammatory reaction. Patients with atheroembolic
acute renal failure often have a normal urinalysis, but the urine may
contain eosinophils and casts
Oliguria refers to a 24-h urine output
<400 mL,
and anuria isthe complete absence of urine formation (<100 mL)
Nonoliguria refers to urine output >400 mL/d
in patients with acute or chronic azotemia.
The dipstick measurement detects only
albumin and givesfalse-positive results at pH >7.0
Quantification of urinary albumin
on a spot urine sample (ideally from a first morning void) bymeasurement of an albumin-to-creatinine ratio (ACR) is helpful in approximating a 24-h albumin excretion rate (AER), where ACR (mg/g) ≈AER (mg/24 h)
Tests to measure total
urine protein concentration accurately rely on precipitation with sulfosalicylic
or trichloracetic acid
Traditionally, healthy individuals excrete
<150 mg/d of total protein and <30 mg/d of albumin.
The glomerular basement membrane traps
most
large proteins (>100 kDa), and the foot processes of epithelial cells (podocytes) cover the urinary side of the glomerular basement membrane and produce a series of narrow channels (slit diaphragms) to allow molecular passage of small solutes and water but not proteins
EVALUATION OF PROTEINURIA
Microalbuminuria
30-300 mg/d or
30-300 mg/g
Macroalbuminuria
300-3500 mg/d or
300-3500 mg/g
Nephrotic range
> 3500 mg/d or
> 3500 mg/g
Hypoalbuminemia in nephrotic syndrome occurs through
excessive urinary losses and increased proximal tubule catabolism of filtered albumin. Edema forms from renal sodium retention and reduced plasma oncotic pressure, which favors fluid movement from capillaries to interstitium
The urinary loss of regulatory proteins and changes in hepatic synthesis contribute to the other manifestations
of the nephrotic syndrome.
A hypercoagulable state may arise from urinary losses of antithrombin III, reduced serum levels of proteins
S and C, hyperfibrinogenemia, and enhanced platelet aggregation. Hypercholesterolemia may be severe and results from increased hepatic lipoprotein synthesis. Loss of immunoglobulins contributes to an increased risk of infection
Hematuria is defined as
two to five RBCs per high-power field (HPF) and can be detected by
dipstick.
A false-positive dipstick for hematuria (where no RBCs are seen on urine microscopy) may occur when myoglobinuria is present, often in the setting of rhabdomyolysis.
Gross hematuria with blood clots usually is not an intrinsic renal process; rather, it suggests a postrenal source in the urinary collecting system
Persistent or significant hematuria
(>3 RBCs/ HPF on three urinalyses, a single urinalysis with >100 RBCs, or gross hematuria) is associated with significant renal or urologic lesions in 9.1% of cases.
The level of suspicion for urogenital neoplasms in
patients with isolated painless hematuria and nondysmorphic RBCs increases with age.
Acute cystitis or urethritis in women can cause
gross hematuria. Hypercalciuria and hyperuricosuria are also risk factors for unexplained isolated hematuria in both children and adults. In some of these patients (50–60%), reducing calcium and uric acid excretion through dietary interventions can eliminate the microscopic hematuria
Hematuria with
dysmorphic RBCs, RBC casts, and protein excretion >500 mg/d is
virtually diagnostic of
glomerulonephritis.
WBC casts with bacteria are indicative of
pyelonephritis. WBCs and/or WBC casts also may be seen in acute glomerulonephritis as well as in tubulointerstitial processes such as interstitial nephritis and transplant rejection
Casts can be seen in
chronic renal diseases. Degenerated cellular casts called waxy casts or broad casts (arising in the dilated tubules that have undergone compensatory hypertrophy in response to reduced renal mass) may be seen in the urine.
true polyuria
(>3 L/d)
Polyuria results from two potential mechanisms:
(1) excretion of nonabsorbable solutes (such as glucose) or (2) excretion of water (usually from a defect in ADH production or renal responsiveness).
The average person excretes between 600 and 800 mosmol of solutes per day, primarily
as urea and electrolytes.
If the urine output is >3 L/d and the
urine is dilute (<250 mosmol/L), total mosmol excretion is normal
and a water diuresis is present. This circumstance could arise from
polydipsia, inadequate secretion of vasopressin (central diabetes
insipidus), or failure of renal tubules to respond to vasopressin
is due to subepithelial deposits, with resulting basement membrane reaction, resulting in the appearance of spike-like projections on silver stain
Membranous glomerulopathy
There is mesangial expansion and endocapillary proliferation with cellular interposition in response to subendothelial deposits, resulting in the
“tram-track” of duplication of glomerular basement membrane
Membranoproliferative glomerulonephritis.
Diabetic nephropathy. In the earliest stage of diabetic nephropathy, only mild mesangial increase and prominent glomerular
basement membranes (confirmed to be thickened by electron microscopy) are present (A). In slightly more advanced stages, more marked
mesangial expansion with early nodule formation develops, with evident arteriolar hyaline (B). In established diabetic nephropathy, there is
nodular mesangial expansion, so-called
Kimmelstiel-Wilson nodules
Water is the most abundant constituent in the body, comprising approximately
50% of body weight in women and 60% in men.
Total body water is distributed in two major compartments: 55–75% is intracellular
(intracellular fluid [ICF]), and 25–45% is extracellular
The ECF is further subdivided into intravascular
(plasma water) and extravascular (interstitial) spaces in a ratio of 1:3.
human body fluid osmolality
between
280 and 295 mOsm/kg.
AVP secretion is stimulated as systemic osmolality increases above a threshold level of ~285 mOsm/kg, above which there is a linear relationship
between osmolality and circulating AVP
Thirst and thus water ingestion are also activated at ~285 mOsm/kg, beyond which there is an equivalent linear increase in the perceived intensity of thirst as a function of circulating osmolality.
AVP acts on renal, V2-type receptors in
the thick ascending limb of Henle and principal cells of the collecting duct (CD), increasing intracellular levels of cyclic AMP and activating protein kinase A (PKA)–dependent phosphorylation of multiple transport proteins
aproximately
two-thirds of filtered Na+-Cl– is reabsorbed by the
renal proximal tubule, via both paracellular and transcellular
The TALH subsequently reabsorbs another 25–30% of filtered Na+-Cl– via the apical, furosemide- sensitive Na+-K+-2Cl– cotransporter.
Approximately 9 L of fluid enter the gastrointestinal tract daily,
2 L by ingestion and 7 L by secretion; almost 98% of this volume is absorbed, such that daily fecal fluid loss is only 100–200 mL.
Evaporation of water from the skin and respiratory tract (so-called
“insensible losses”) constitutes the major route for loss of solute-free
water, which is typically
500–650 mL/d in healthy adults.
orthostatic tachycardia
(an increase of >15–20 beats/min upon standing), and orthostatic hypotension (a >10–20 mmHg drop in blood pressure on standing).
the urine Na+ concentration is typically
<20 mM in nonrenal causes of hypovolemia, with a urine osmolality of >450 mOsm/kg. The reduction in both GFR and distal tubular Na+ delivery may cause a defect in renal potassium excretion, with an increase in plasma K+ concentration.
hypovolemia and a hypochloremic alkalosis due to vomiting, diarrhea, or diuretics will typically have a urine Na+ concentration >20 mM and urine pH of >7.0, due to the increase in filtered HCO3 –;
the urine Cl– concentration in this setting is a more accurate indicator of volume status, with a level <25 mM suggestive of hypovolemia. The urine Na+ concentration is often >20 mM in patients with renal causes
is the most appropriate resuscitation fluid for normonatremic or hyponatremic patients with severe hypovolemia; colloid solutions such as intravenous
albumin are not demonstrably superior for this purpose.
Hypernatremic patients should receive a hypotonic solution, 5% dextrose if there has only been water loss (as in diabetes insipidus), or hypotonic saline (1/2 or 1/4 normal saline) if there has been water and Na+-Cl– loss.
Isotonic, “normal” saline (0.9% NaCl, 154 mM Na+)
Patients with severe hemorrhage or anemia should receive red cell transfusions, without increasing the hematocrit beyond 35%.
Hypovolemic Hyponatremia
UNa >20 Renal losses Diuretic excess Mineral corticoid deficiency Salt-losing deficiency Bicarbonaturia with renal tubal acidosis and metabolic alkalosis Ketonuria Osmotic diuresis Cerebral salt wasting syndrome
UNa <20 Extrarenal losses Vomiting Diarrhea Third spacing of fluids Burns Pancreatitis Trauma
euvolemic
hyponatremia.
UNa >20
Glucocorticoid deficiency Hypothyroidism Stress Drugs Syndrome of inappropriate antidiuretic hormone secretion
Thiazide diuretics cause hyponatremia via a number of mechanisms,
including polydipsia and diuretic-induced volume depletion.
Notably, thiazides do not inhibit the renal concentrating mechanism, such that circulating AVP retains a full effect on renal water retention.
In contrast, loop diuretics, which are less frequently associated with hyponatremia, inhibit Na+-Cl– and K+ absorption by the TALH, blunting the countercurrent mechanism and reducing the ability to concentrate the urine. Increased excretion of an osmotically active nonreabsorbable or poorly reabsorbable solute can also lead to volume depletion and hyponatremia;
important causes include glycosuria, ketonuria (e.g., in starvation or in diabetic or alcoholic ketoacidosis), and bicarbonaturia (e.g., in renal tubular acidosis or metabolic alkalosis, where the associated bicarbonaturia leads to loss of Na+).
Hypervolemic Hyponatremia
UNa >20
Acute or chronic
renal failure
UNa <20
Nephrotic syndrome
Cirrhosis
Cardiac failure
is the most frequent cause of euvolemic hyponatremia
The syndrome of inappropriate antidiuresis (SIAD)
Strictly speaking, patients with SIAD are not euvolemic but are subclinically volume-expanded, due to AVP-induced water and Na+-Cl– retention; “AVP escape” mechanisms invoked by sustained increases
in AVP serve to limit distal renal tubular transport, preserving a modestly hypervolemic steady state.
Serum uric acid is often low (<4 mg/dL) in patients with SIAD, consistent with suppressed proximal tubular transport in the setting of increased distal tubular Na+-Cl– and water transport; in contrast, patients with hypovolemic hyponatremia will often be hyperuricemic
SIAD
also occurs with malignancies, most commonly with
Small-cell lung carcinoma (75% of malignancy associated SIAD); ~10% of patients with this tumor will have a plasma Na+ concentration of <130 mM at presentation
SIAD is also a frequent complication of certain drugs,
most commonly the selective serotonin reuptake inhibitors (SSRIs). Other drugs can potentiate the renal effect of AVP, without exerting direct effects on circulating AVP levels
Hyponatremia can occasionally occur in patients with a very low intake of dietary solutes. Classically, this occurs in alcoholics whose sole nutrient is beer, hence the diagnostic label of
beer potomania; beer is very low in protein and salt content, containing only 1–2 mM of Na+
The initial CNS response to acute
hyponatremia
is an increase in interstitial pressure, leading to shunting of ECF and solutes from the interstitial space into the cerebrospinal fluid and then on into the systemic circulation. This is
Early symptoms hyponatremia can include
nausea, headache, and vomiting. However, severe complications can rapidly evolve, including seizure activity, brainstem herniation, coma, and death.
key complication of acute hyponatremia is normocapneic or hypercapneic respiratory failure; the associated hypoxia may amplify the neurologic injury. Normocapneic respiratory failure in this
setting is typically due to noncardiogenic, “neurogenic” pulmonary edema, with a normal pulmonary capillary wedge pressure.
Women, particularly before menopause, are much more likely than men to develop encephalopathy and severe neurologic sequelae.
The recreational drugs
cause a rapid and potent induction of both thirst and AVP, leading to
severe acute hyponatremia
Molly and ecstasy, which share an
active ingredient (MDMA, 3,4-methylenedioxymethamphetamine),
cause a rapid and potent induction of both thirst and AVP, leading to
severe acute hyponatremia
Persistent, chronic hyponatremia results in an efflux of organic osmolytes (creatine, betaine, glutamate, myoinositol, and taurine)
from brain cells; this response reduces intracellular osmolality and the
osmotic gradient favoring water entry.
This reduction in intracellular osmolytes is largely complete within 48 h, the time period that clinically
defines chronic hyponatremia
chronic hyponatremia does not fully protect patients
from symptoms, which can include vomiting, nausea, confusion, and
seizures, usually at plasma Na+ concentration <125 mM
Rapid correction of hyponatremia (>8–10
mM in 24 h or 18 mM in 48 h)
is also associated with a disruption in integrity of the blood-brain barrier, allowing the entry of immune
mediators that may contribute to demyelination.
The lesions of ODS classically affect the
pons, a structure wherein the delay in the reaccumulation of osmotic osmolytes is particularly pronounced;
clinically, patients with central pontine myelinolysis can present 1 or more days after overcorrection of hyponatremia with paraparesis or quadriparesis,
dysphagia, dysarthria, diplopia, a “locked-in syndrome,” and loss of consciousness.
in order of frequency, the lesions of extrapontine
myelinolysis can occur in the cerebellum, lateral geniculate body, thalamus, putamen, and cerebral cortex or subcortex
Clinical presentation of ODS can, therefore, vary as a function of the extent and localization of extrapontine myelinolysis, with the reported development of
ataxia, mutism, parkinsonism, dystonia, and catatonia.
Relowering of plasma Na+ concentration after overly rapid correction can prevent or attenuate ODS
Serum glucose should also be measured; plasma Na+ concentration falls by
~1.6–2.4 mM for every 100-mg/dL increase in glucose,
the ultimate “gold standard” for the diagnosis of hypovolemic hyponatremia
is the demonstration that plasma Na+ concentration corrects after hydration with normal saline.
A urine osmolality <100 mOsm/kg
is suggestive of polydipsia; urine osmolality >400 mOsm/kg indicates that AVP excess is playing a more dominant role
Patients with hyponatremia
due to decreased solute intake
(beer potomania) typically have urine
Na+ concentration <20 mM and urine osmolality in the range of <100 to the low 200s. Finally, the measurement of urine K+ concentration
is required to calculate the urine-to-plasma electrolyte ratio, which is useful to predict the response to fluid restriction
patients with chronic hyponatremia, present for
> 48 h, are less likely to have severe symptoms. Second, patients with chronic hyponatremia are at risk for ODS if plasma Na+ concentration is corrected
by >8–10 mM within the first 24 h and/or by >18 mM within the first 48 h.
Insensible Losses
~10 mL/kg per day: less if ventilated, more if febrile
Many patients with SIAD respond to combined therapy with
oral furosemide, 20 mg twice a day (higher doses may be necessary in renal insufficiency), and oral salt tablets;
furosemide serves to inhibit the renal countercurrent mechanism and blunt urinary concentrating ability, whereas the salt tablets counteract diuretic-associated natriuresis.
is a potent inhibitor of principal cells and can
be used in patients whose Na levels do not increase in response to furosemide and salt tablets.
However, this agent can be associated with a reduction in GFR, due to excessive natriuresis and/or direct renal toxicity; it should be avoided in cirrhotic patients in particular, who are at higher risk of nephrotoxicity due to drug accumulation.
Demeclocycline
are highly effective in SIAD and in hypervolemic hyponatremia due to heart failure or cirrhosis, reliably increasing plasma Na+ concentration due to their “aquaretic” effects (augmentation of free water clearance).
AVP antagonists (vaptans)
Most of these agents specifically antagonize the V2 AVP receptor; tolvaptan is currently the only oral V2 antagonist to be approved by the U.S. Food and Drug
the only available intravenous vaptan,
is a mixed V1A/V2 antagonist, with a modest risk of hypotension due
to V1A receptor inhibition. Therapy with vaptans must be initiated in
a hospital setting, with a liberalization of fluid restriction (>2 L/d) and
Conivaptan
Abnormalities in liver function tests
have been reported with chronic tolvaptan therapy; hence, the use of this agent should be restricted to <1–2 months.
Treatment of acute symptomatic hyponatremia should include
hypertonic 3% saline (513 mM) to acutely increase plasma Na+ concentration by 1–2 mM/h to a total of 4–6 mM; this modest increase is typically sufficient to alleviate severe acute symptoms
The administration of supplemental oxygen
and ventilatory support is also critical in acute hyponatremia, in the event that patients develop acute pulmonary edema or hypercapneic
respiratory failure
AVP antagonists do not have an approved role in the management of acute hyponatremia.
hyponatremia can be safely reinduced or
stabilized by the administration of the AVP agonist
desmopressin acetate (DDAVP) and/or the administration of free water, typically intravenous D5W; the goal is to prevent or reverse the development of ODS
Alternatively, the treatment of patients with marked hyponatremia can be initiated with the twice-daily administration of DDAVP to maintain constant AVP bioactivity, combined with the administration
of hypertonic saline to slowly correct the serum sodium in a more controlled fashion, thus reducing upfront the risk of overcorrection
is, in turn, the most common gastrointestinal
cause of hypernatremia.
Diarrhea
Notably, osmotic diarrhea and viral gastroenteritides
typically generate stools with Na+ and K+ <100 mM, thus leadingto water loss and hypernatremia;
is characterized by renal resistance to AVP, which can be partial or complete
Nephrogenic DI (NDI)
can also cause polyuria and NDI; calcium signals directly through the calcium-sensing receptor to downregulate Na+, K+, and Cl– transport
by the TALH and water transport in principal cells,
hypercalcemia.
thus reducing renal concentrating ability in hypercalcemia
Lithium causes NDI by multiple mechanisms, including
direct inhibition of renal glycogen synthase kinase-3 (GSK3), a kinase thought to be the pharmacologic target of lithium in bipolar disease; GSK3 is required for the response of principal cells to AVP.
As in hyponatremia, the symptoms of hypernatremia are predominantly neurologic.
Altered mental status is the most frequent manifestation, ranging from mild
confusion and lethargy to deep coma.
The sudden shrinkage of brain cells in acute hypernatremia may lead to parenchymal or subarachnoid hemorrhages and/or subdural hematomas; however, these vascular complications are primarily encountered in pediatric and neonatal
patients
Many patients with hypernatremia are
polyuric; should an osmotic diuresis be responsible, with excessive excretion of Na+-Cl–, glucose,
and/or urea, then daily solute excretion will be >750–1000 mOsm/d (>15 mOsm/kg body water per day
a water deprivation test is unnecessary in hypernatremia; indeed, water deprivation is absolutely contraindicated in this setting,
given the risk for worsening the hypernatremia.
Patients with NDI will fail to respond to DDAVP, with a urine osmolality that increases by <50% or <150 mOsm/kg from baseline, in combination with a normal
or high circulating AVP level; patients with central DI will respond to DDAVP, with a reduced circulating AVP. Patients may exhibit a partial response to DDAVP, with a >50% rise in urine osmolality that nonetheless fails to reach 800 mOsm/kg; the level of circulating AVP will help differentiate the underlying cause
Patients with central DI should respond to the administration of intravenous, intranasal, or oral DDAVP. Patients with NDI due to lithium may
reduce their polyuria with amiloride (2.5–10 mg/d), which decreases entry of lithium into principal cells by inhibiting ENaC
may reduce polyuria due to NDI, ostensibly
by inducing hypovolemia and increasing proximal tubular water reabsorption.
Thiazides
have been used to treat polyuria associated with NDI,
reducing the negative effect of intrarenal prostaglandins on urinary concentrating mechanisms;
Occasionally, nonsteroidal anti-inflammatory drugs
(NSAIDs)
however, this assumes the risks of
NSAID-associated gastric and/or renal toxicity
