Kit Delgado mcd2027@columbia.
edu
Renal Pathophysiology (Based on Small Group Cases)
Acute Renal Failure
Clinical Presentation
Oliguria (<400 ml/ day) over the
course of a weeks to months
with:
Hypovolemic state
¾ GI loss, hemorrhage,
dehydration, diuretics,
pancreatitis
Low Cardiac Output:
¾ CHF, arrythmias, etc.
Renal vasoconstrictive states:
¾ Advanced liver disease
(cirrhosis with ascites)
Vasodilatory states:
¾ Sepsis, antihypertensives
Intrinsic decrease in renal
perfusion:
¾ NSAID use or ACE inhb. use
(in patients with CHF, cirrhosis,
nephritic syndrome or any
other salt retaining state)
Physical:
¾ Orthostatic hypotension,
decreased venous pressure,
decresed skin tugor, dry
mucous membranes, and
decreased sweating
Labs
¾ BUN/Cr ratio > 20/1 (High!
Enhanced due to
increased FF and
because BUN
reabsorption is
concentration dependent
and Cr is never
reabsorbed)
¾ Uosm > 400
¾ UNa < 20 (Extremely low!)
Exception: if patient was
on diuretics, then could
be 50 or so.
¾ FeNa < 1% (U/P for Na
over U/P Cr). Indicates
that the tubules are very
active and that the oliguric
state has to do with the
decrease in GFR)
¾ Urine sediment
unremarkable
Differential Diagnosis
¾ Rule out intrinsic and post-renal
causes (BUN/Cr elevated, UNa
<20 except in the case of
diuretics, unremarkable urine
casts)
Pathophysiology Management
Pre-Renal Azotemia ¾ If ECF vol. or cardiac
function returned to
¾ Abruptly decreased GFR due to normal Æ the decline
decreased renal perfusion in GFR should be
reversed
¾ Manifested by oliguria with an increase
in BUN and Cr (and BUN/Cr) with
inherently normal renal function
Renal vasoconstriction
¾ In volume depletion the decreased in RBF
is more severe than the decrease in GFR
Æ FF increased (GFR/RBF)
¾ Mediated by renin-AII, sympathetic
response
¾ In “hepatorenal syndrome” source of
vasoconstriction not known
Increased Na absorption
¾ Higher FF increases the diving force for
proximal tubule reabsorption
¾ Aldosterone secretion has also been
stimulated leading to increased Na
reabsoprtion in collecting ducts
Clinical Presentation
¾ Severe oliguria of variable
duration followed by period
of increased urine output
and improvement in GFR
¾ Also a non-oliguric form
(>400 ml per day) which is on
the rise (same lab values as
for the oliguric version) as
seen with Aminoglycosides
Labs
¾ BUN/Cr < 15/1 Æ B/c salt
and water not reabsorbed
properly Æ no rapid
increase of urea
concentration to cause
enhanced back diffusion.
¾ Uosm < 350; Urine
specific gravity ~ 1.010:
Indicates defective ability
to concentrate urine
¾ UNa > 20 Salt not
reabsorbed properly
(Exception: radiographic
contrast)
¾ FeNa > 1% Indicates
tubules are not active in
reabsorbing sodium.
(Exception: radiographic
contrast)
¾ Casts and tubular cells
in urine sediment from
renal injury –
INDIVIDUAL TYPES
DETERMNINE Ddx
Rhabdomyolysis:
¾ Elevated uric acid, K, PO4,
Decreased Ca
¾ Heme and myoglobin in
urine
¾ Casts common
¾ 50% non-oliguric
¾ BUN/Cr could decrease
due to excess Cr spilling in
the blood
Differential Diagnosis
Acute Tubular Necrosis (NO
PROTEINURIA + GRANULAR OR
PIGMENTED CASTS)
¾ Most common cause of ARF
¾ Ischemic (Trauma, crush
sydrome with myoglobinuria,
massive hemorrhage, Gram
negative sepsis)
¾ Nephrotoxins
(Aminoglycosides, vancomycin,
radiographic contrast, Cisplatin,
Carbon tetrachloride, Ethylene
glycol, Non-traumatic
rhabdomyolysis)
Acute nephritic syndromes
(PROTEINURIA AND RBC CASTS
in urine)
¾ Post- Streptococcal GN (recent
strep. throat)
¾ SLE (skin rash, joint pain)
¾ HSP (RMSF-like rash); IgA
¾ Bacterial endocarditis (heart
murmur)
¾ Goodpasture’s (hemoptysis)
¾ HUS (uncooked beef), TTP,
Postpartum renal failure
¾ Idiopathic rapidly progressive
GN
Acute interstitial nephritis (NO
PROTEINURIA, NO CASTS, FEW
WHITE OR RED CELLS, SOME
EIOSINOPHILS)
¾ Drug-related
¾ Idiopathics
Vascular diseases
¾ Malignant hypertension
¾ Scleroderma
¾ Unilateral renal artery occlusion
¾ Bilateral renal vein thrombosis
(In glomerular disease get many
casts, heavy proteinuria)
Pathophysiology Management
Intra-Renal Causes of ARF ¾ Remove inciting cause
¾ Dialysis
¾ Abruptly decreased GFR from damage
to glomerular, tubular, interstitial, or
renal vascular tissue
¾ Mechanisms: Obstruction, “Back-leak”
of filterate, afferent vasoconstriction,
alterations in glomerular permeability
or combo
¾ Severe decreases in renal blood flow are
important for the initiation of the syndrome
¾ Three phases of ATN: Prodromal
(depends on etiology), Oliguric (most
lethal time, although doesn’t occur in all
patients), Post-Oliguric (gradual return to
normal but tubular dysfunction may
persist)
ATN
¾ Ischemia: necrosed cells slough off Æ
obstruction
¾ Precipitates Æ obstruction
¾ Very high levels of AII can actually cause
AFFERENT vasoconstriction Æ GFR
goes down further Æ but salt cannot be
reabsorbed due to damaged tubules Æ
Na hits macula densa Æ positive
feedback for more renin secretion Æ even
more AII
Special cases:
¾ Rhabdomyolysis (see labs)
¾ Radiographic contrast
(vasoconstrictive role Æ increased salt
retention)
¾ Aminoglycosides (Non-oliguric
presentation predominates; distinguish
from sepsis)
Difference from Chronic Renal Failure
¾ ARF pts. have more of a problem
regulating volume (oliguria) compared to
CRF pts who have polyuria
¾ Most pts w/ ATN die of volume
overload from oliguria (eg. Pulmonary
edema)
¾ ATN pts have Hyperkalemia b/c of
decreased urine flow rate
¾ ATN frequently w/ tissue injury Æ
“Hypercatabolic state” Æ rapid onset of
uremic syndrome
Clinical Presentation Labs Differential Diagnosis Pathophysiology Management
Oliguria ¾ UNa > 40. High urine Na ¾ Renal Stones Post-Renal Failure ¾ Removal of obstruction
in presence of oliguria is ¾ BPH
typical of post-renal. ¾ Bladder/Pelvic tumors ¾ Abrupt decline in GFR due to an
obstruction of outflow from the kidney
¾ Uosm <350 Key: Use ultrasound to detect ¾ Bilateral obstruction of ureters or of
hydronephrosis – confirms post- the urethra
¾ FeNa > 4% renal when there is oliguria, and ¾ 5% of ARF cases
UNa > 40
¾ BUN/Cr > 15%
Functional abnormalities:
¾ Increase in hydrostatic pressure going
back up Æ decrease in ultrafiltration
pressure Æ decreased filtration rate

¾ Permeability of tubules to Na increases Æ

leakiness prevents the tubule from
decreasing the luminal Na to its normal
level + for some reason rate of active Na
absorption is decreased throughout the
nephron Æ increased Na excretion
Regulation of Volume
Clinical Presentation
(Case 1, p.4)
Hx: Diarrhea, Nausea, Decreased
Appetite
PE: Signs of volume depletion:
orthostatic hypotension, dry mucous
membranes, poor skin turgor, no
axillary sweat
(Case 2, p. 5)
Hx: SOB
PE: Signs of CHF
Gets digoxin and diuretic
Labs Differential Diagnosis Pathophysiology Management
Blood: GI salt and water loss, decreased Na intake ¾ Administer IV saline
BUN: 25
Cr: 1.1 Decreased renal perfusion Æ increased
Na: 128 renin release Æ AII Æ
K: 3.2 (hypokalemic)
Cl: 102 Proximally:
HCO3: 15 (acidodic) ¾ Constriction of afferent arteriole Æ
increased FF Æ increased peritubular
Urine: oncotic pressure Æ increased driving
UNa: 2 force for absorption (as evidenced by
K: 15 (below normal) increased BUN/Cr of 25)
PH:4.8
Distally:
¾ Increased Aldosterone Æ increase
distal reabsorption of Na
Together Æ Low Sodium Output (UNa = 2)
Blood: Congestive Heart Failure If patient takes NSAID for
BUN: 22 --> 63 on digoxin and headache or injury Æ could
diuretics ¾ Low cardiac output Æ arteriole lead to abrupt decline in
Cr: 1.3 --> 2.5 underfilling Æ increased renin-AII Æ Na GFR from PG inhibition Æ
Na: 130 retention Æ positive Na balance Æ uninhibted AII Æ instant
K: 3.4 expansion of extracellular volume Æ appearance of edema
Cl: 100 restoration of cardiac function Æ
HCO3: 27 arterial underfilling ceases Æ AII, Aldo,
sympathetic tone decrease Æ New
Urine: Steady State (Na input = Na output)
Urine vol.: 680 Æ 1500 ¾ Further decompensation of heart function
UNa: 2 Æ 60 (can’t interpret causes above process to repeat again
b/c on diuretic) ¾ In severe CHF, patient will remain in
K: 68 high R-AII state with positive Na
Cr: 150 (low) Æ 80 balance despite massive ECF vol. (JGA
keeps sensing vol. depletion)
¾ Note: Addisonian patients with heart
failure can get edema indicating
proximal mechanism for Na retention is
sufficient
Admin. diuretic and digoxin
¾ Patient was in renal failure and got worse
¾ BUN/Cr rose Æ indicates even more renin
release (but not in same proportion
because of increased reabsorption of
BUN)
¾ If UNa starts to fall Æ indicates diuretic
resistance (from countervailing forces
like increased proximal reabsorption)
Clinical Presentation Labs
(Case 3, p. 6) ¾ Because of malnutrition
often present in
Hx: Chronic alcoholic w/ alcoholics Æ less BUN to
Cirrhosis start off with Æ BUN/Cr
isn’t as high as it should
PE: Ascites, pedal edema, clear be
lungs
(Case 4, p.7) UNa > greater than intake
Marked volume depletion and
hypotension
(Case 4) Brief period of low UNa but
then resumes output of Na
equal to input
Differential Diagnosis Pathophysiology Management
Cirrhosis
Uncomplicated cases
¾ Increases in hepatic venous pressure
Æ primary salt retention
Ascites in Advanced Cases
¾ Portal hypertension Æ increased
hydrostatic pressure Æ transudation of
fluid into peritoneal cavity
¾ Decreased intravascular volume from
decreased albumin
¾ Peripheral vasodilation (vasodilators
(NO) are not cleared in liver disease)
Hypoalbuminemia doesn’t have too great effect
on proximal tubular reabsorption
Addison’s Disease
No mineralcorticoids Æ no aldosterone Æ No
Na+ reabsorption Æ DT and CD Æ increase in
urine sodium
Primary Mineralcorticoid Excess
(Cushing’s, Primary Hyperaldosteronism?)
Increased aldosterone Æ Na retention Æ
increased volume Æ which is sensed by carotid
sinus, JGA Æ downregulated catecholamines,
renin Æ compensatory decrease in proximal
reabsorption of NA Æ eventually
oversaturates distal tubules ability to
reabsorb NA Æ urine Na rises Æ steady
state
Clinical Presentation Labs Differential Diagnosis Pathophysiology Management
¾ Edema ¾ Heavy proteinuria (>3 Nephrotic Syndrome and
g/day) Glomerulonephritis
¾ Hypoalbumenmia
Immune injury to glomerulus Æ proteinuria Æ
Salt retention

Ex. Lipoid nephrosis in children: GFR normal,

increased permeability Æ hypoalbunemia Æ
decrease in plasma oncotic pressure Æ
edema Æ activation of Na retention systems

In nephrotic syndrome patients with normal

plasma volume Æ found GFR decreased with
reduced renin but still had Na retention Æ
indicates that many of these patients were
not able to excrete a salt load = the main
cause of salt retention (common in
advanced glomerularnephritis; problem not
in proximal tubules Æ indicates local factors
at play.)
Regulation of Tonicity of Body Fluids
Clinical Presentation
(Case 1, p.8)
24 y.o female w/ HX of Lasix
abuse
PE: Signs of volume depletion.
Denies fever, vomiting, diarrhea.
Labs Differential Diagnosis Pathophysiology Management
Serum: Hyponatremia Diuretic-Induced Hyponatremia
Na: 127 ¾ GFR down (elevated Cr)
K: 3.0 ¾ Decreased fluid delivered to ¾ Patient is hypo-osmolar (Free water input
Cl: 94 thick ascending limb (b/c > Free water ouput)
HCO3: 30 volume depletion Æ elevated
BUN: 30 proximal tubule reabsorption via ¾ Lasix causes you to excrete half normal
Cr: 1.2 rennin-AII Æ elevated BUN/Cr) saline.
pH: 7.49 ¾ Poisened thick ascending
PCO2: 47 limb (diuretic) ¾ To avoid hyponatremia need to be able to
PO2: 80 ¾ Most importantly ADH is up retain the capacity to excrete a large
Osm: ? volume of dilute urine. With diuretic, the
Other stuff going on… patient has contracted the homeostatic
range.
Na(2) + K(2) + gluc/18 +
Hypokalemic Metabolic Alkalosis
[BUN/2.8 only factor in
¾ ADH levels are high as indicated by
situations like dialysis when
Low K Uosm 380 > Posm 265 This is because
urea falls rapidly]
¾ Not intake issue the diuretic Æ volume depletion Æ
¾ Renal (increase Na flow, aldo) increased ADH secretion relative to
127(2) + 3(2) + 90/18 = 265
Æ K excretion serum osmolaity.
¾ Shift: Met. Alkalosis Æ shifts K
Urine
ouit of blood Æ into cells ¾ Patient should be thirsty (despite the fact
Na: 44
that she is hypo-osmolar) Æ because of
Osm: 380
Metabolic Alkalosis arteriole underfilling Æ activated the renin-
¾ Generation: Elevated Cr for her, AII system.
decreased HCO3 excretion
¾ Maintanence: Volume depletion,
hypokalemia, renal failure
Clinical Presentation
(Case 2, p. 9)
75 y.o. female with CHF presents
with increasing pedal edema of 1
month. Has required increasing
doses of diuretics.
PE: CHF signs, orthostatic
hypotension Æ Hypovolemic
(Case 2, p. 9, #4)
75 y.o. man with CHF with marked,
but stable pedal edema. Weight
has been stable for the last three
weeks.
Labs Differential Diagnosis Pathophysiology Management
Serum Hyponatremia Hyponatremia in Congestive Heart Failure
Na: 126 ¾ GFR reduced While on Diuretic
K: 3.1 ¾ High renin state
Cl: 90 ¾ Diuretic ¾ This patient developed hyponatremia
HCO3: 32 ¾ Volume depletion Æ ADH because free water intake > free water
BUN: 22 (activation of volume output. Primarily b/c volume receptors
Cr: 1.5 receptors Æ release of ADH. Æ ADH secretion and because the
Glu: 130 There patients require a lower diuretic constricted the homeostatic
osmolality to turn on ADH range.
Urine secretion and have higher
24h: 900 ADH levels at osmolarities ¾ See (Volume Case 2., p 5). Progressively
Uosm: 400 above their set point). decreasing cardiac output Æ sensed
volume depletion Æ high renin, ADH state
Æ expansion of extracellular volume Æ
some improvement of cardiac function on
Starling curve Æ downregulation of renin
and ADH Æ new salt and water steady
state
¾ The patient has had decompensating
cardiac function Æ spike in renin Æ
increasing edema. Thirst is also
activated.
Serum Sodium (126)
¾ Doesn’t tell you anything about salt
balance!
¾ But, tells you that free water input >
free water output)
Uosm (400)
¾ Indicates a concentrated urine,
therefore ADH must be elevated.
Serum Congestive Heart Failure in Steady State
Na: 137
BUN: 17 ¾ This man is in compensated salt
Cr: 1.5 balance as indicated by the stable pedal
edema and stable weight and UNa of 80.
Urine ¾ Na 137 indicates that he is in free water
Na: 80 balance also. (No sensed volume
depletion as above Æ therefore ADH is
not being secreted at high levels Æ
free water output can match input)
Clinical Presentation
(Case 3, p. 9)
32 y.o male falls resulting in
compound fractures, skull
trauma. The comatose man taken
to hospital with becomes febrile.
D5 ½ NS with 20 meq/LKCl at 75
cc/hr = 2 liters of half normal
saline per day
+ antiobiotics
(Case 4, p 10)
60 yo female complains of “lack of
energy” for two months
PE: No orthostatic signs,
pulmonary edema, or edema.
Labs Differential Diagnosis Pathophysiology Management
th
7 hospital day: Water balance Hypernatremia
Serum Intake
Na: 158 ¾ 1 liter of water ¾ The patient has become volume i.e. salt
K: 3.2 depleted (Una <20) and water depleted
Cl: 119 Output (Na >158 – hyperosmolar by definition)
HCO3: 29 ¾ Increased insensible losses: over the past week
BUN: 61 fever, GI, wound loss, water
Cr: 1.3 vapor, urine ¾ If Urine Osm below 265 definitely
Glucose: 130 Ddx: indicative of Diabetes Insipidus Æ
¾ Uosm of 450 rules out urine osm more dilute than serum Æ
Urine: Diabetes Insipidus (which via absent ADH (trauma) or decreased
Na: 3 could have been caused by the response to ADH (nephrogenic)
Uosm: 450 skull fracture Æ ability to
excrete such large volumes of Other causes of DI
urine to point of hypernatremia ¾ No Marked Hypokalemia (which inhibits
Æ due to lack of ADH) ADH)
Na balance ¾ Urine is not maximally ¾ No Hypercalcemia Æ in ADH resistant DI
Intake concentrated Æ probably ¾ No Lithium, democlocyline Æ neprhogenic
¾ 1 liter of saline Æ 150 because medullary DI
meq/L of Na/day = normal concentration gradient has
diet been reduced by long term Tx for DI is to volume deplete
Output exposure to ADH which will
¾ Low (UNa 3) Æ from continue to absorb dilute urine
volume depletion (high from the collecting duct directly
BUN/Cr) into the medullary space.
¾ Osmotic diuresis (no signs of
elevated glucose: which would
obligate water to it, increase
medullary wash out, impair Na
reabsorption, and predispose
hypokalemia)
(2nd values after patient given Water intake not greater than 20L Chronic Hyponatremia due to SIADH ¾ Paradoxically, treat
2L of saline IV) (the max the kidney can excrete in with saline and Lasix
one day) ¾ Uosm 420 indicates that ADH is
Serum present
Na: 122 Æ 121 Serum osmolality not greater than ¾ UNa of 60 indicates that salt retention
Cl: 86 Æ 86 normal (a condition when ADH is mechanism hasn’t been turned on yet. If
K: 3.4 Æ 3.1 stimulated – ex. Hyperglycemia) constant weight, then must equal intake).
HCO3: 27 Æ 26
BUN: 8 Æ 8 No signs of volume depletion After saline administration…
Cr: 1.1 Æ 1.0 (volume receptors activate ADH) ¾ Patient excreted saline without
correcting the plasma sodium
Urine No renal failure concentration because have an ectopic
Osm: 420 Æ 500 source of ADH. The BUN/Cr is low. Not
Na: 60 Æ 169 Therefore differential left to: edematous, but these patient is primed to
Urine vol: 980 Æ 1500 ¾ Hypothyroidism excrete a volume load.
¾ Hypoglutocorticoidism
CXR ¾ SIADH ¾ In a normal person with a S Na of 122,
Vague density in right lower would expect a Urine Osm of 100
lung field. ¾ With severe SIADH one could see urine
volumes osm of 1000
¾ She stopped at 500 due to a wash out
of the renal medulla
Acid-Base
Clinical Presentation
Case 1: 40 y.o man w/
myocarditis, acute onset of CHF.
Edema, rales. BP 70/40 = shock.
Case 2. 42 y.o woman vomiting,
carpopedal spasm
Case 3. 60 y.o man w/ cirrhosis
presents w/ confusion,
increasing ascites, orthostatic
hypotension
Tx: Lactulose for
encephalopathy, loop diuretic for
ascites
Labs
Case 1: initial presentation
PH 7.32, pCO2 28, HCO3 15, K
5.5
= compensated met. acidosis
After Tx w/ diuretics:
PH 7.48, pCO2 44. HCO3 35, K
3.2
= compensated met. alkalosis
Initial presentation
PH 7.80, pCO2 20, HCO3 39, K
3.0
= mixed: metabolic alkalosis
with respiratory alkalosis
Una 2 = evidence of volume
depletion
UpH 5.5
Given Demerol:
PH 7.50, pC02 55, P02 68
Nasogastric tube placed:
HCO3 rises to 42
Initial presentation
PH 7.45, pCO2 30, HCO3 20
= Chronic Respiratory
Alkalosis
PH 7.48, pCO2 = 52, HCO3 36
= Metabolic Alkalosis w/
respiratory compensation
Differential Diagnosis
Anion Gap = 20 Æ Lactic acidosis
likely
Rule out non-renal generation of
alkalosis (i.e. vomiting, or exogenous
HCO3)
Diuretic induced hypokalemia
Generation – vomiting
Maintenance – volume depletion
Spasms – related to alkalosis Æ
hypocalcemia Æ tetanus Æ pain Æ
hyperventilation
Generation – Negative salt balance
from the diuretic
Maintanence – effective intravascular
volume depletion
Pathophysiology Management
Acute CHF with Metabolic Alkalosis Æ Initially given diuretics Æ
Metabolic Alkalosis w/ Diuretic Tx loss of weight, resolution of
edema
¾ After diuretics, no signs of non-renal H+
loss
¾ Therefore, can be explained by elevated
aldosterone (elevated BUN/Cr would be
evidence) and increased distal sodium
delivery (diuretic) Æ secreting more H+
Æ therefore absorbing more HCO3
¾ Become slightly hypokalemic Æ
maintenance of alkalosis
Mixed Alkalosis Æ Metabolic Alkalosis ¾ Receives low dose
Demerol to relieve
¾ Patient is hyperventilating due to the pain pain
¾ Demerol also has the effect of not only DO’s
relieving pain from the spasms Æ also ¾ Address hypokalemia
depresses respiratory drive Æ and volume depletion
stopping the respiratory alkalosis (result: decreased
serum pH, increased
¾ Don’t expect the PC02 to go above 60 urine pH)
because the hypoxic respiratory drive to ¾ KCl IV
breath will kick in ¾ NaCl IV
¾ Nasogastric tube Æ sucks out H+ = DON”Ts
non-renal generation of met. alkalosis ¾ Spironolactone – b/c
Æ HCO3 rises Æ volume depletion has she’s volume depleted
not been addressed Æ therefore
kidneys cannot correct the problem Special cases
¾ HCl IV only in
emergent cases where
there are seizures,
arrythmias from
alkalosis
Chronic Respiratory Alkalosis in Cirrhosis
¾ Cirrhotics hyperventilate due to increased
biogenic amines
Clinical Presentation
Case 4. 50 y.o. man with diarrhea
for 4 days, has only managed
oral intake
In ER becomes hypotensive Æ
shock Æ given fluids:
Case 5. 4 y.o girl takes a bunch of
aspirin comes to hospital in
confused state.
Labs Differential Diagnosis Pathophysiology Management
Initial presentation Anion Gap = 9 Diarrhea Progressing to Lactic Acidosis
PH 7.34, pCO2 32, HCO3 18
= Metabolic Acidosis w/
respiratory compensation
PH7.27, PCO2 20, HCO3 10 Anion Gap = 18
PH 7.62, PCO 20, HCO3 22 Salicylate intoxication can cause Salicylate Intoxication
= Acute Respiratory Alkalosis respiratory alkalosis and
metabolic acidosis
A few hours later…
PH 7.58, pCO2 18, HCO3 18 Anion gap = 13
= Chronic Respiratory
Alkalosis
Clinical Presentation
Case 6: 24 yo w/ diabetes
mellitus for routine followup
Labs Differential Diagnosis
PH 7.35, pCO2 31, HCO3 18, K Anion Gap = 8
5.9 Therefore cannot be diabetic
Compensated metabolic ketoacidosis!
acidosis
Ddx:
Cr 2.2, BUN 20, UpH 5.5 ¾ RTA’s proximal or Type IV
¾ Distal RTA (rule out b/c UpH
is not elevated (>6). Distal
area last to reabsorb Æ no
way to compensate)
¾ Distal always wasting HCO3,
and if HCO3 is stable, it’s at a
cost due to bone wasting
¾ Associated with autosomal
dominant defect in children,
Amphoterecin,
aminoglycosides, lithium,
autoimmune disorders,
nephrocalcinosis, urinary tract
obstruction, renal transplant
¾ Chronic Renal Failure (rule out
b/c Cr not high enough)
¾ Diarrhea (not present)
Pathophysiology Management
Renal Tubular Acidosis ¾ Need less HCO3 to
correct acidosis for
Type VI RTA: someone with Type
¾ Urine is acidic, K is elevated IV RTA compared to
¾ Therefore, likely to be Type IV RTA (which proximal RTA
is typically found in diabetics and patients
with chronic interstitial nephritis) ¾ If person with distal
RTA give
¾ Hyporeninemic hypoaldosteronism supplemental HCO3,
(evidenced by normal BUN/Cr) Æ little increase in
hyperkalemia Æ inhibits urinary HCO3 loss Æ
ammoniagenesis Æ prevents adequate indicated proximal
NH4+ excretion Æ despite normal function ok
acidic urine, have decreased buffering
capacity Æ less H+ secretion Æ less
HCO3 generation Æ acidosis ensues
¾ Similar mechanism for acidosis seen in
primary adrenal failure
¾ Acid ingestion increases ammonia
synthesis and synthesis by a saturable
mechanism
¾ Therefore, the other way to have low
ammonia Æ acidosis is in chronic renal
failure (less nephrons)
Cannot rule out proximal RTA because there
are two types:
¾ Steady state with low UpH (distal tubule
can compensate)
¾ Non-steady state with HCO3 wasting Æ
high UpH
¾ 15% of the filtered HCO3 load is
excreted into urine b/c of partial failure
of proximal tubule to secret H+
¾ Associated w/ amyloidosis, multiple
myeloma, cystic kidney dz, drug ingestion,
and caddium and lead poisining
¾ To rule it out: Add HCO3 to push the
patient out of steady state (raise it by 4
units or so), the patient should be able
to reabsorb it they don’t have proximal
RTA
Potassium
Clinical Presentation
Case 1: 40 y.o. man w/ alcoholic
cirrhosis, w/ diarrhea, moderate
ascites, on furosomide Æ weight
loss.
Diarrhea gets worse…but given
K, diuretic
continued…hypotension
Labs
Initial presentation
Na 133, K 2.9, pH 7.58, pCO2
44, HCO3 33, BUN 20, Cr 1.4
Na 133, K 6, pH 7.3, pCO2 30,
HCO3 15, BUN 50, Cr 3.5,
urine output 10cc/hr
Differential Diagnosis Pathophysiology Management
Hypokalemia following severe volume
depletion, diuretic use
Intake
¾ Low K
Output
¾ Volume depleted (increased aldosterone
(BUN/Cr up) Æ increased K excretion
¾ Metabolic Acidosis with respiratory
compensation Æ increased K excretion
¾ Diuretic Æ Na rich flow Æ Increase in
K+ excretion
¾ Non-renal K loss: vomiting, diarrhea
Shifts
Low K: Causes of K shifts into cell
¾ Alkalosis
¾ Increased B sympathetic stimulation
¾ Increase insulin
High K: Causes of K out of cell
¾ Metabolic acidosis (via decrease in Na/K
ATPase activity)
¾ Decreased insulin
¾ Decreased Beta activation (Beta-blockers)
After diarrhea gets worse…
¾ K intake up from IV
¾ Still volume depleted (increased Aldo
favors losing K, but urine flow rate down
Æ hold onto K, this is more important)
¾ Compensated metabolic acidosis (favors
increased K in blood)
¾ Decreased urine output Æ favors holding
onto K
Clinical Presentation
Case 2: 20 y.o. male with crush
injury, significant hemorrhage,
hypotensive.
Fluid resuscitated with 3 L
normal saline, bleeding
controlled, BP stabilizes; given
HCO3.
Transfused with 3 units of
packed red blood cells
Case 3: 60 y.o man with cirrhosis
presents with encephelopathy,
increasing ascites. On normal
diet, no meds, orthrostatic on PE.
Started on lacutulose and loop
diuretic Æ improved ascites and
mental status; worsened
orthostasis
Labs
Initial presentation
Na 138, K 6.8, Cl 105, HCO3
12, pH 7.29, pCO2 25, Hct 38,
Urine output 5 cc/hr
Urine output unchanged.
Na 146, K 5.4, Cl 110, HCO3
18, pH 7.34, pCO2 32, Hct 25
BP 130/80. Urine output
remains low. EKG shows
peaked T waves; Na 145, K
6.9, Cl 115. HCO3 23
Na 134, K 3.5, Cl 100, HCO3
27, pH 7.42, pCO2 41, Urine K
60
Na 128, K 2.7, Cl 87, HCO3 35,
pH 7.49, pCO2 48
Differential Diagnosis Pathophysiology Management
Hyperkalemia following Crush Injury Fluid resucitation, control
bleeding, prophylatic K
Intake – N/A binder per rectum before
giving transfusion
Renal output
¾ Oliguria flow (favors holding on to K)
Non-renal output
¾ No diarrhea, vomiting
Shifts
¾ Rhabdomyolysis Æ causes spillage of
K into the blood
¾ Shock Æ lactic acidosis Æ favors K
shift out of cells
Plasma K goes down…
¾ Less acidodic
But it is still elevated b/c:
¾ Urine output is unchanged
Hyperkalemic
¾ Transfused RBCs Æ some undergo cell
lysis Æ spike in K, no change in urine
output
¾ Arrhythmia
Advanced Cirrhosis Treated with Diuretic, K sparing diuretic or
Lactulose Æ Hypokalemia lower dose loop diuretic
would have been better
¾ K is at the low end of normal (probably choice
from high aldosterone level associated
with ascites Æ effective volume depletion)
¾ Urine K of 60 indicates he’s in steady
state
Hypokalemic
Intake – don’t know anything
Renal Output
¾ Increase in Na rich flow Æ K out
¾ Worsened volume depletion Æ
increase in aldosterone Æ K out
Non-renal Output
¾ Lactulose Æ diarrhea Æ K out
Shift
¾ Metabolic Alkalosis (actually favors K
retention – small effect)
Chronic Renal Failure
Clinical Presentation
Case 1:48 y.o woman
hospitalized for Hx of headaches,
nausea and vomiting, nocturia,
but no frequency, dysuria,
hematuria. Passed kidney stone
three years prior. Taken
salicylates.
PE: BP 160/100, pulse 92.
Labs
Na 136,
K 5.1,
HCO3 18, (low)
BUN 68, (significantly
elevated)
Cr 8.1, (Extremely high)
Liver Function Tests normal,
albumin 3.5,
Calcium 8.1, (low)
Phosphate 7.1 (elevated)
Normal Urinalysis:
Urine specific gravity – 1.009
(normal osmolality)
Protein 1+
Examination of sediment – no
red cells or casts, a few white
cells
Differential Diagnosis
Drug induced chronic interstitial
nephritis
Papillary necrosis – but would expect
pain from papilla dislodging
Rule out glomerulonephritis – b/c
minimal proteinuria and no RBC
casts
Pathophysiology Management
Chronic Renal Failure from Salicylates
Urinalysis is normal
¾ Although she has low GFR (Cr 8.1,
assume steady state), the remaining
nephrons are working well
¾ Nephron # not related to GFR until renal
reserve used up (usually 40% of
nephrons).
¾ Metabolic Alkalosis – from nausea and
vomiting
Clinical Presentation
Case 2: 42 y.o. man with ESRD
from chronic glomerulonephritis.
On low salt diet, prior to dialysis
had high salt meal…
Next time before dialysis he has 6
beers…
Goes for his monthly checkup…
Goes to ER with anterior chest
pain, been taking digoxin…
Labs
Cr clearance 5 ml/min (very
low)
Expect Na to be normal as long
as thirst mechanism is intact
Weight should be elevated
Hyponatremia expected
Weight should be elevated
K should be normal because of
the large buffer inside cells
Hct: 23 (low)
Ca: 8.2 (low)
PO4: 8.0 (high)
Differential Diagnosis
Hct. Ddx:
¾ Decreased erythopoetin
¾ Dilution
¾ Prior disease
¾ Had been taking aluminum PO4
binders Æ anemia, bone
disease
¾ Uremic gastritis
Ddx:
¾ Digoxin cleared by kidney Æ
should be on a lower dose
¾ Toxicity Æ arrthymia
¾ Uremic Syndrome
Pathophysiology Management
ESRD with Dialysis
¾ ADH actually not elevated, this is one
of the only times this happens with
hyponatremia
¾ PO4 is retained when GFR goes down
Æ rises independent of changes in
volume Æ causes “metastatic
calcification” Æ brings plasma Ca
down Æ PTH rises
¾ Also as PO4 levels rise Æ vitamin D (an
inhibitor of PTH) levels go down Æ this
stimulates synthesis and release of PTH
¾ As renal function decreases begin losing
the ability to hydroxylate 25-OH
choleciferol (which is isomerized and
hydroxylated Vitamin D) Æ this decreases
the absorption of Ca, PO4 in the gut Æ
osteomalacia in adults, rickets in children
¾ In early stages of renal failure Æ PTH
reduces reabsorption of PO4, increases
reabsoprtion of Ca in kidney Æ PO4, Ca
maintained at normal level, but as disease
progresses Æ get higher levels of PTH Æ
increases bone reabsorption of Ca and
PO4 Æ osteitis fibrosa cystica bone
disease
Uremic syndrome:
¾ Build up of “toxins”
¾ Disturbed mental function – lethargy,
confusion, seizures, asterixis
¾ Serositis Æ presents are pericarditis
(pleural rub and effusion)
¾ Uremic gastritis Æ exacerbates anemia
Glomerulonephritis
Clinical Presentation
Case 1: 60 y.o. man presents with
“flu.”Had rash on ankle two
weeks prior to respiratory Sx,
also noticed “puffy” face, shoes
tight. Used NSAIDs frequently.
PE: BP 180/110, 2+ pitting edema,
rales
Case 2: 51 y.o male w/ leg edema
of two months duration, non-
remarkable medical history, not
on any meds
Labs
Na 136, K 4.8, Cl 100, pCO2
22, BUN 48, Cr 3.6
Urinalysis: “tea colored urine,” 3
+ protein, RBC casts
Serum complement low
ASLO titer high
Cr 1.2, BUN 12
Serum albumin 2.6 (low)
Total bilirubin, SGOT, SGPT,
LDH, alkaline phosphatase
normal (not cirrhosis)
Urinalysis: 4+ protein, no
glucose, no RBC casts, many
hyaline casts, a few oval fat
bodies
Differential Diagnosis Pathophysiology Management
Acute Renal Failure (needs be Acute Renal Failure from Post-
confirmed with ultrasound to see if Streptococcal Glomerulonephritis
kidneys normal size) due to:
¾ Not pre-renal b/c BUN/Cr normal
¾ Acute Neprhitic Syndrome ¾ Nephritic syndrome with ephritic range
(most likely b/c of RBC casts, proteinuria
post infectious onset, serum
complement low)
¾ ATN
¾ AIN
¾ Vascular lesion
Leg Edema Ddx: ¾ Not in renal failure
¾ CHF
¾ DVT
¾ Nephrotic Syndrome (supported
by the low albumin, urinalysis)
¾ Etc.
Nephrotic Ddx :
¾ multiple myeloma
¾ Glomerular
Hypertension
Clinical Presentation
Case 1: 50 yo man w/ 170/100 BP,
PE normal
Starts chlorthalidone, returns 4
wks later…BP 160/98
Dose increased Æ month later BP
did not change
Given KCl and told to eat fresh
fruits
Discontinues diuretic, starts
enalapril…BP 160/90
Enalapril + Diuretic…BP 120/80
Labs
EKG: LVH
CXR: No detectable
abnormalities (therefore not
dilated)
Urine analysis: 1+ proteinuria,
no cells
Na 142, K 4, Cl 104, CO2 25,
BUN 10, Cr 1
Na 138, BUN 14, Cr 1
K down to 3, HCO3 up to 32,
BUN up to 30, Cr 1
K up to 3.8, HCO3 down to 28
K up to 4.0
Differential Diagnosis Pathophysiology Management
Hypertension Treated with Diuretic and ACE
Inhibitor
¾ Chlorthalidone = thiazide Æ distal tubule
Æ works on Na-Cl transporter
¾ Lowered BP a little bit by putting patient at
a negative salt balance
¾ Expect weight to be down
¾ Plasma sodium went down b/c free water
input > free water output
¾ BUN/Cr went up – b/c he’s sensing the
volume depletion Æ increased proximal
tubular reabsorption
¾ GFR hasn’t changed (Cr still 1)
¾ Hypokalemic Metabolic Acidosis:
Increase in Aldosterone plus a diuretic
Æ increased Na to distal nephron Æ
lumen negative membrane potential Æ
enhanced H+ secretion
¾ When K is replaced in hypokalemic
metabolic acidosis Æ improve HCO3
excretion
¾ ACE Inhibitor Æ decreased AII Æ
decreased proximal tubular reabsoprtion
¾ Can concluded that b/c poor response
Æ at this point he is not in a high renin-
AII state
¾ Diuretic and ACE inhibitor have a
synergistic effect
¾ Diuretic by itself Æ results high renin
state by causing volume depletion
¾ ACE inhibitor by itself Æ problem is
that when you are at volume expanded
steady state, renin effects are already
suppressed
¾ K probably rises b/c of ACE inhibitors
effect on reducing aldosterone(?)
Clinical Presentation
Case 2. 65 y.o. female following
up after acute MI…BP 190/100,
sequalae of HTN,
Given captopril ,,,140/80
Labs Differential Diagnosis Pathophysiology Management
Na 140, K 4.5, Cl 102, HCO 27, Two most common causes: Renal Artery Stenosis Hypertension
BUN 20, Cr 2 ¾ Artherosclerotic plaques
Urinalysis normal ¾ Fibromuscular dysplasia (seen ¾ The kidneys are different in size b/c they
Ultrasound: 1 kidney 11 cm, in young women) act like sacs that fill with pressure. The
other 6cm smaller kidney is hypoperfused and is
Screening: therefore smaller
¾ ACE inhibitor cause big
K up to 5.5, BUN up to 30, Cr increase in renin which is
up to 3 more marked in RAS than in
essential hypertension

Case 3: 30 y.o. man brought to
the ER w/ SOB, mailaise. BP
240/132. Signs of CHF.
CXR: cardiomegaly, haziness in Malignant Hypertension caused by Renal If you drop the patient to BP
lung fields Failure 140/90, will kill him due to
Na 130, K 6, HCO3 17 hypoperfusion…need to do
BUN 90, Cr 9, it slowly
¾ Na 130 b/c free water intake < free water
Urine 3+ protein
output Æ can’t excrete a large volume of
200 rbc/hpf and 2 wbc/hpf ¾ Nitroprusside (short
dilute urine b/c he’s in renal failure
acting, easy to titrate)
¾ HCO3 17 Æ metabolic acidosis (Anion
¾ Captopril
Gap = 11), should be a higher anion gap
since his Cr is above 6
¾ K 6 Æ Hyperkalemic b/c urine flow is
down, acidosis causes shift out

Case 4: 35 y.o. female presents
w/ 148/92, in good health, goes to
gym 6X per week.
Na 147, K 3.9, Cl 92, HCO3 32,
BUN 10, Cr 0.6
Ddx: Hypokalemic Metabolic Alkalosis ¾ Tx: Spironolactone
¾ Diuretic abuse (ask if on meds)
¾ Pirmary Aldosteronism (check ¾ However, she is Hypernatremic –
renin, aldosterone and increased ADH
mineralcorticoid levels in
general)
¾ ADH set point moved up by
hypernatremia

Need blood gas

Case 5: 66 y.o. patient with long
standing and poorly controlled
hypertension…BP 170/100
Placed on amlodipine and
enalapril…3 months BP 118/76
CXR: cardiomegaly
EKG: LVH
Normal electrolytes, Cr 3.5
Urine 24 hr: 1.3 g Cr ¾ Amlodopine = Ca channel blocker
¾ Renal fxn may have worsened due to
small stenosis
CXR: normal heart size
Na 140, K 5, Cl 103, HCO3 19,
Cr 7 ¾ Urine Cr excretion being equal on both
Urine 24 hr: albumin .8 g, 1.3 g days indicates he was in steady state
Cr
¾ Metabolic Acidosis – b/c his GFR went
down Æ renal failure Æ ability to make
ammonia exceeded Æ he
decompensated
Clinical Presentation Labs Differential Diagnosis Pathophysiology Management
Case 6: 48 y.o male w/ insulin K 7.5 Potential causes for elevated K ¾ Tx: Any diuretic other
dependent diabetes and HTN has than spironolactone
BP 120/75 but has risen to 140/90 Need: Input – N/A
over a few months. Given ¾ Urine K Output
atenelol. ¾ ABG ¾ Renal: GFR has fallen off,
¾ Blood glucose lower flow state Æ less K
¾ Serum Cr excretion
Shift
¾ Insulin may not be sufficient
Æ K goes out of the cell
¾ B-blocker Æ K goes out