Renal organ system

Cortical and
juxtamedull
ary
nephrons

Renal corpuscle

Normal glomeruli

The glomerular filtration barrier

1. Capillary
endothelium
2. Basement
membrane
3. Epithelial layer
4. Filtration slits of
the podocytes

Tubul
ar
lumen

Tubular
cell

Interstitial
fluid

Distribution of body H2O

Intracellular fluid
Extracellular fluid

Intracellular fluid (ICF)

Is 2/3 of TBW
The major cations of ICF are k+ and
Mg++
The major anions of ICF are protein
and organic phosphates

Extracellular fluid
Is 1/3 of TBW
Composed of interstitial fluid and
plasma
The major cation of ECF is Na+
The major anions are Cl- and HCO3-

Plasma
1/4 of ECF
1/12 of TBW (1/4 1/3)
The major plasma proteins are
albumin and globulins

Interstitial fluid
Is 3/4 of ECF
is 1/4 of TBW
Its composition = plasma except
that has a little protein
Interstitial fluid is an ultrafiltrate of
plasma

60-40-20 rule
TBW is 60% of body weight
ICF is 40% of body weight
ECF is 20% of body weight

Measuring the volumes of the fluid

compartments
Dilution method: a known amount of
substance is given whose volume of
distribution is the body fluid
compartment of interest
1. Tritiated water: marker for TBW
2. Mannitol, inulin: markers for ECF
3. Radiolabeled albumin marker for
plasma volume

Exercise
A patient is injected with 500 mg of
mannitol. After 2- hour equilibration period,
the [mannitol] in plasma is 3.2 mg/100 mL.
During the equilibration period, 10% of the
mannitol is excreted in urine. What is the
patients ECF volume?
Volume = amount/concentration =
Amount injected Amount excreted/ [] =
500 mg 50 mg 3.2 mg/100 ml = 450
mg/ 3.2 mg/100 mL = 140.625 dL = 14.1 L
15

Clearance
Volume of plasma cleared of a
substance per unit time (mL/24 hrs)
C = UV/P (mL/min or mL/24 hr)
Where:
U = Urine concentration (mg/mL)
V = Urine volume/time (mL/min)
P = Plasma concentration
(mg/mL)

Exercise
If plasma [Na+] is 140 mEq/L, the
urine [Na+] is 700 mEq/L, and the
urine flow rate is 1 mL/min, what is
the clearance of Na+?
CNa+ = [U]Na+ x V/[P]Na+ =
700 mEq/L x 1 mL/min 140 mEq/L
=
5 mL/min

Clearance, reabsorption,
secretion
Cx < GFR: net tubular reabsorption of
X
Cx > GFR: net tubular secretion of X
C = GFR: no net secretion or
reabsorption

Measurement of GFR: clearance of inulin

Inulin is freely filtered

Not reabsorbed or secreted by renal
tubules

GFR calculation
GFR = Cinulin = [U]inulin x V/[P]inulin
(mL/min)
[U]inulin = urine concentration of
inulin (mg/mL)
V = urine flow rate (mL/min)
[P]inulin = plasma concentration of
inulin (mg/mL)

Exercise
Inulin is infused in a patient to achieve a
steady-state plasma concentration of 1 mg/mL.
A urine sample collected during 1 hour has a
volume of 60 mL and a inulin concentration of
120 mg/mL. What is the patients GFR?
GFR = [U]inulin x V/[P]inulin =
120 mg/mL x 60 mL/hr 1 mg/mL =
120 mg/mL x 1 mL/min 1 mg/mL = 120
mL/min

Estimates of GFR with BUN

and serum [creatinine]
Both BUN and serum [creatinine]
increase when GFR decreases
In prerenal azotemia BUN increases
> serum creatinine
In prerenal azotemia BUN/creatinine
ratio increases (> 20:1)

Measurement of ERPF:
clearance of paraaminohippuric acid (PAH)
PAH is filtered and secreted by the
renal tubules
All PAH entering kidney is excreted
Clearance of PAH is used to measure
ERPF
Clearance of PAH measures effective
RPF and underestimates true RPF by
10%

ERPF calculation
ERPF = CPAH

[U]PAH x V/[P]PAH

Where:
CPAH = clearance of PAH (mL/min)
[U]PAH = urine [PAH} (mg/mL)
V = urine flow rate (mL/min)
[P]PAH = plasma [PAH] (mg/mL)

Measurement of Renal blood flow

(RBF)

RBF = ERPF/1
hematocrit

Filtration fraction
Is the fraction of RBF filtered across
the glomerular capillaries
Filtration fraction = GFR/RBF
Normally about 0.20 (20% of the RPF
is filtered)

Increases in the filtration

fraction
Increase the [protein] in the tubular
capillary blood
Increase reabsorption in the proximal
tubule

Decreases in the filtration

fraction
Decrease the [protein] of peritubular
capillary blood
Decrease reabsorption in the
proximal tubule

Determining GFR: Starling

forces

29

Changes in glomerular
dynamics: GFR, RBF, FF
1. Constriction of
afferent arteriole
2. Constriction of
efferent arteriole
3. Increased plasma
[protein]
4. Decreased plasma
[protein]
5. Ureteral obstruction

Summary of changes in glomerular

dynamics
Effect

RFP

GFR

Filtration
fraction
(FF)

Afferent arteriole
constriction

No change

Efferent arteriole
constriction

Increased plasma
[protein]

No change

Decreased plasma
[protein]

No change

Constriction of ureter

No change

Tubuloglomerular feedback
Increased renal arterial pressure
leads to increased delivery of fluid to
the macula densa
The macula densa senses the
increased load and causes
constriction of nearby afferent
arteriole
Resistance increases to maintain
constant blood flow

Renal vascular disease

Decrease renal blood flow
Increase the release of renin
Renal artery fibromuscular dysplasia
(hyperplasia)
Renal artery atherosclerosis

Free-water clearance
Is used to estimate the ability to
concentrate or dilute the urine

Free water
Produced in the diluting segment
(thick ascending loop of Henle) of the
kidney

Calculation CH O
2

CH2O =V-COSM
Where:
CH2O = freewater clearance
(mL/min)
V = urine flow rate (mL/min)
COSM = osmolar clearance
(UOSMV/POSM) [mL/min]

Example
If the urine flow rate is 10 mL/min, urine
osmolarity is 100 mOsm/L and plasma
osmolarity is 300 mOsm/L, what is the freewater clearance?
CH2O =V COSM
CH2O = 10 mL/min (COSM = 100 mOsm/L X
10 mL/min 300 mOsm/L)
CH2O = 10 mL/min 3.33 mL/min = +6.7
mL/min

CH2O and ADH

CH2O with ADH: CH2O < 0 (retention
of free water)
CH2O without ADH: CH2O > 0
( excretion of free water)
Isotonic urine: CH2O = 0 (loop
diuretics)

Reabsorption and secretion

rates

Filtered load: GFR x Px

Excretion rate: V x Ux
Reabsorption: filtered excreted
Secretion: excreted filtered

Glucose clearance
Glucose at a normal plasma level is
completely reabsorbed in proximal
tubule
At plasma concentrations of 160-200
mg/dL glycosuria begins
At 350 mg/dL all transporters are
fully saturated

Amino acid clearance

Na+ dependent contransporters in
proximal tubule reabsorb all amino
acids
At least 3 distinct carrier systems
Deficient neutral amino acid
transporter: Hartnups disease

Renin-agiotensin-aldosterone
system

Renin
Stimuli for release?
1. Decreased blood pressure in JG cells
2. Decreased Na+ delivery to macula
densa cells
3. Increased sympathetic tone (1
receptors)
. Function?
Convert angiotensinogen into
angiotensin

1
1

Angiotensin I
Converted to angiotensin II by
angiotensin converting enzyme (ACE)
Location of ACE?
Pulmonary vascular endothelium
Increases in response to chronic
inhibition
Function of ACE?
1. Conversion of AT I to AT II
2. Degradation of bradykinin

Angiotensin II
Stimulates AT receptors on vascular smooth muscle:
vasoconstriction
Constricts efferent arteriole of glomerulus:
Increases FF to preserve renal function in low volume
states
Activates aldosterone synthase
Stimulates ADH release from neurohypophysis
Increases proximal tubule Na+/H+ activity
Increases H2O reabsorption
Affects baroceptor function to limit reflex bradycardia
Stimulates hypothalamic thirst center

Aldosterone
Source?
Zona glomerulosa of adrenal gland
Mechanism?
1. Increases Na+ channels and Na+/K+
pump insertion in principal cells of DT
2. Upregulates principal cell K+ channels
3. Upregulates intercalated cell H+ channels
4. Increases Na+ and H2O reabsorption
5. Enhances K+ and H+ excretion
6. Increases the expression of ACE genes

Mechanism of aldosterone

ADH
Mechanism?
1. Increases H2O channel insertion in
principal cells
2. Increases H2O reabsorption
. Responsible for corticopapillary gradient
(urea, Na+)
. Involved in countercurrent exchange
. ADH present: concentrated, low volume
urine
. ADH absent: diluted, high volume urine

Mechanism of action of ADH

50

Atrial natriuretic factor

Source?
1. Atria in response to increased volume
. Mechanism?
1. Increased cGMP
2. Increases GFR
3. May antagonize aldosterone
4. Decreases renin
. Brain natriuretic factor (BNP): marker of
CHF

Erythropoietin
Released in response to hypoxia
from endothelial cells of peritubular
capillaries
Increases erythropoiesis

Prostaglandins
Paracrine secretion vasodilates
afferent arterioles to increase GFR
Involved in AIDS-induced renal failure

K+ shifts out of cells: hyperkalemia

Insulin deficiency: Na+/K+ ATPase
-adrenergic antagonists: Na+/K+
ATPase
Acidosis, severe exercise: K+/H+
exchanger
Hyperosmolarity
Digitalis
Cell lysis

K+ shifts into cells:

hypokalemia
Insulin: Na+/K+ ATPase
-adrenergic agonists: Na+/K+
ATPase
Alkalosis: K+/H+ exchanger
Hypoosmolarity

Renal H+ handling, acid base

physiology

Excretion of H+ as titratable
acid
Depends on the amount of urinary
buffer present (H2PO4-)
In urine the H+ combines with
filtered HPO4- to form H2PO4 H2PO4- is excreted as titratable acid
Aldosterone increases H+ -ATPase

Excretion of H+ as NH4+
The amount of H+ excreted as NH4+
depends on:
1. The amount of NH3 produced by renal
cells
2. Urine pH
. H+ excretion as NH4+ increases as the
pH of tubular fluid decreases
. Adaptive increase in NH3 synthesis
occurs in acidosis

H+ excretion as NH4+

60

Acid base disturbances

Metabolic acidosis
Metabolic alkalosis
Respiratory acidosis
Respiratory alkalosis

Acid-base physiology
pH

PCO2

[HCO3-]

Metabolic
acidosis

Metabolic
alkalosis

Respiratory
acidosis

Respiratory
alkalosis

Serum anion gap

[Na+] ([Cl-] + [HCO3-])
Normal range is 8-16 mEq/L
Represents unmeasured anions in
serum
1. Phosphate
2. Citrate
3. Sulfate
4. Protein

Normal anion gap alteration

When the [Cl-] is increased to replace
HCO3-

Increased anion gap

alteration
When the [] of an unmeasured anion
is increased to replace HCO3-

Metabolic acidosis
Increased [H+]
Due to overproduction or ingestion of
a fixed acid or loss of base
HCO3- decreases as it is used as a
buffer

Features of metabolic
acidosis
HCO3-: decreased
PCO2: decreased
[H+]: increased

Causes of normal anion gap

metabolic acidosis
Diarrhea , glue sniffing
Type I (distal) renal tubular acidosis
1. Defect in collecting tubules ability to excrete H+
2. Hypokalemia, risk for Ca++ kidney stones
. Type II (proximal) renal tubular acidosis
1. Defect in proximal tubule HCO3- reabsorption
2. Hypokalemia, hypophosphatemic rickets
. Type IV (hyperkalemic) renal tubular acidosis
1. Hypoaldosteronism/lack of response to
aldosterone
2. Hyperkalemia,NH4 excretion in proximal tubule

Causes of high anion gap metabolic

acidosis

Ketoacidosis
Lactic acidosis
Chronic renal failure (uremia)
Salicylate intoxication
Methanol/formaldehyde intoxication
Ethylene glycol intoxication
Iron tablets, INH

Compensation for metabolic

acidosis
Hyperventilation

Metabolic alkalosis
Decreased arterial H+
Due to loss of fixed H+ or gain of
base
As a result HCO3- increases

Features of metabolic
alkalosis
HCO3-: increased
PCO2: Increased
H+: decreased

Causes of metabolic
alkalosis

Vomiting
Hyperaldosteronism
Loop and thiazide diuretics
Antacid use

Compensation for metabolic

alkalosis
Hypoventilation

Special situation: volume contraction

metabolic alkalosis
The renin-angiotensin II-aldosterone
system activates
The reabsorption of HCO3- increases
The metabolic alkalosis worsens

Respiratory acidosis
Caused by a decrease in respiratory
rate and retention of CO2
PCO2 increases
H+ and HCO3- Increase

Causes of respiratory
acidosis
Sedative-hypnotics, general
anesthetics
Neurologic diseases (GBS, ALS)
Airway obstruction
Adult respiratory distress syndrome
COPD

Compensation for respiratory

acidosis
Increased excretion of H2PO4- and
NH4+
Increased reabsorption of new HCO3 Increased PCO2 supplies more H+ to
the renal cells for secretion
Increased HCO3- normalizes pH

Respiratory alkalosis
Caused by an increased respiratory rate
Decreased PCO2 results in a decrease in
H+ and HCO3 Features:
1. PCO2: decreased
2. H+: decreased
3. HCO3-: decreased
4. Hypocalcemia

Causes of respiratory
alkalosis

Pneumonia and pulmonary embolus

High altitude
Psychogenic
Salicylate intoxication

Compensation for respiratory

alkalosis
Decreased excretion of H2PO4- and
NH4+
Decreased PCO2 causes a deficit of
H+ in the renal cells for secretion
Decreased reabsorption of new HCO3-

Casts in urine
Indicate renal disease

RBC casts
Glomerulonephritis
Ischemia
Malignant hypertension

White blood cell casts

Tubulointerstitial inflammation
Acute pyelonephritis
Transplant rejection

Granular casts
Acute tubular necrosis

Waxy casts
Advanced renal disease
Chronic renal failure

Hyaline casts
Non specific

Fatty casts
Nephrotic syndrome

Glomerular disorders
Nephrotic syndrome
Nephritic syndrome
Rapidly progressive
glomerulonephritis

Normal glomerulus

Nephritic syndrome
Inflammatory process
When it involves glomeruli:
Leads to hematuria and RBCs casts in
urine
Associated with:
1. Azotemia
2. Oliguria
3. Hypertension
4. Proteinuria < 3.5 g/day

Acute post-streptococcal
glomerulonephritis
Most frequently seen in children
Peripheral and periorbital edema
Resolves spontaneously
Light microscope:
1. Enlarged, hypercellular glomeruli with
neutrophils
2. lumpy-bumpy appearance
. Electron microscope: subepithelial immune
complexes, humps
. Immunofluorescence: granular pattern

Epithelial
immunocomplexes

Granular appearance on
immunofluorescence (IF)

Rapidly progressive (crescentic)

glomerulonephritis
Poor prognosis
Etiology:
1. Goodpasture syndrome: linear IF
2. Wegener granulomatosis: c-ANCA
3. Microscopic Polyarteritis: p-ANCA
. Microscopy and IF: crescent-moon shape
1. Fibrin and plasma proteins
2. Glomerular parietal cells, mononuclear
cells

Linear pattern on IF typical of

Goodpastures syndrome

Crescent proliferation

Crescent appearance on IF

Diffuse proliferative
glomerulonephritis
Etiology:
1. Lupus (MCC of death)
2. Membranous proliferative glomerulonephritis
3. Can present as nephrotic syndrome
. Microscopy:
1. Subendothelial DNA-anti DNA
Immunocomplexes
2. wire looping of capillaries
3. Granular IF

Subendothelial immunocomplex
deposits

Bergers disease (IgA

glomerulonephropahty)
Often presents with a URI or acute
gastroenteritis
Increased synthesis of IgA
Microscopy and IF:
Immunocomplex deposition in
mesangium

Alport's syndrome

Mutation of type IV collagen

Split basement membrane
Nerve disorders
Ocular disorders
Deafness

Nephrotic syndrome

Massive proteinuria > 3.5 g/day

Frothy urine
Hyperlipidemia, fatty casts
Edema
Associated with thromboembolism
Increased risk of infection

Membranous glomerulonephritis
(diffuse membranous glomerulopathy)
MCC of adult nephrotic syndrome
Etiology: dugs, infections, lupus, solid
tumors
LM: diffuse capillary and GBM
thickening
EM: spike and dome appearance
with superficial deposits
IF: granular pattern

Minimal change disease (lipoid

nephrosis)
MCC of nephrotic syndrome in children
May be triggered by recent
infection/immune stimulus
Due to GBM polyanion loss
LM: normal glomeruli
EM: foot process effacement
Selective loss of albumin, not globulins
Responds to steroids

Normal glomerulus

Renal amyloidosis
Associated with multiple myeloma,
chronic conditions, TB, rheumatoid
arthritis
LM (Congo red): apple-green
birefringence

Diabetic
glomerulonephropahty
Etiology:
1. Nonenzymatic glycosylation (NEG) of GMB
2. Increased permeability of filtration barrier
3. Thickening
4. NEG of efferent arterioles: increased GFR
5. Mesangial expansion
. Microscopy:
1. Mesangial expansion
2. GBM thickening
3. Nodular glomerulosclerosis
4. Kimmestiel-Wilson nodules

Kimmestiel-Wilson nodules

Membranoproliferative
glomerulonephritis

Can present as nephritic syndrome

Usually progresses slowly to CRF
Type I: associated with HBV > HCV
Type II: C3 nephritic factor
Microscopy: Subendothelial
immunocomplexes
Granular IF
EM of type I: tram track appearance
(GBM splitting due to Mesangial ingrowth)
EM of type II: dense deposits

Focal segmental
glomerulosclerosis
Segmental sclerosis and hyalinosis
MC in HIV patients
More severe in HIV patients

Kidney stones
Can lead to hydronephrosis and
pyelonephritis
Tx and prevention: fluid intake
1. Calcium
2. Ammonium magnesium phosphate
(struvite)
3. Uric acid
4. Cystine

Calcium stones
MC kidney stones: 75-85%
Calcium oxalate, calcium phosphate or both
Oxalate crystals: ethylene glycol, vitamin c
excess
Radiopaque stones
Etiology:
1. Cancer
2. Hyperparathyroidism
3. Hypervitaminosis D
4. Milk alkali syndrome

Ammonium magnesium phosphate

(struvite) stones

2nd MC kidney stone

Radiopaque/radiolucent stones
Worsened by alkaluria
Caused by infection with urease +
organisms
Can form staghorn calculi that can
facilitate UTIs

Uric acid stones

Strong association with
hyperuricemia
Often seen as a result of diseases
with increased cell turnover
Radiolucent stones

Cystine stones
Most often secondary to cystinuria
Hexagonal shape
May for cystine staghorn calculi
rarely
Faintly radiopaque stones
Tx: alkalinization of urine

Autosomal dominant polycystic

kidney disease
Multiple, large, bilateral cysts destroying
parenchyma
Enlarged kidneys
Mutation in APKD1 or APKD2
Flank pain, hematuria, hypertension, urinary
infections, progressive renal failure
Associated with polycystic liver, berry
aneurysms and mitral prolapse
Death results from renal failure or
hypertension

Autosomal recessive polycystic

kidney disease
Infantile presentation in parenchyma
Associated with congenital hepatic
fibrosis
Significant renal failure in utero can
lead to Potters sequence
Hypertension, portal hypertension,
progressive renal insufficiency

Other cysts
Simple: benign, incidental finding, In cortex
Dialysis-related: cortical and medullary
Medullary cystic disease:
1. Medullary cysts
2. Cysts may lead to fibrosis and progressive
renal insufficiency
3. Urinary concentrating defects
4. Ultrasound shows small kidneys
5. Poor prognosis

Renal cell carcinoma

MC renal malignancy
Invades IVC and spreads via the blood
Metastasizes to lung and bone
Ages 50-70
Smoking and obesity are risk factors
Von Hippel-Lindau (chromosome 3) is
a risk factor
Polygonal clear cells of tubular origin

Clinical features
Hematuria
Palpable mass
Secondary polycythemia
Flank pain
Fever, weight loss
Preneoplastic syndromes:
1. Ectopic erythropoietin
2. Ectopic ACTH
3. Ectopic PTHrp
4. Ectopic prolactin

Transitional cell carcinoma

MC tumor of urinary tract system
Painless hematuria suggests bladder
cancer
Associated with:
1. Phenacetin
2. Smoking
3. Aniline dyes
4. Cyclophosphamide

Wilms tumor
MC renal malignancy of early childhood
Huge palpable flank mass and hematuria
May be associated with hemihypertrophy
syndromes (Beckwith-Wiedemann
syndrome)
Embryonic glomerular structures
Associated with deletion of WT1 (chrom 11)
WAGR complex: tumor, aniridia, GU
malformation, mental-motor retardation

Acute pyelonephritis
Affects the cortex with relatively
sparing of glomeruli/vessels
White cell casts in urine
Fever
CVA tenderness
Nausea, vomiting

Chronic pyelonephritis
Coarse, asymmetric corticomedullary
scarring
Blunted calyx
Tubules can contain eosinophilic
casts (thyroidization)

Drug-induced interstitial
nephritis
Acute interstitial renal inflammation
Pyuria + azotemia 1-2 weeks after administration
Fever, rash
Hematuria, eosinophiluria
CVA tenderness
Drugs acting as haptens inducing hypersensitivity:
1. NSAIDs
2. Penicillin derivatives
3. Sulfonamides
4. Rifampin

Acute tubular necrosis

MCC of acute renal failure in hospital
Self-reversible but fatal if left untreated
Cause: ischemia, myoglobinuria (crush injury),
toxins
Phases: initiating event, maintenance (low urine),
recovery (2-3 weeks)
Death MC occurs during initial oliguric phase
Pathology:
1. Loss of cell polarity
2. Epithelial cell detachment
3. Necrosis
4. Granular casts

Renal papillary necrosis

Sloughing of renal papillae
Gross hematuria, proteinuria
May be triggered by recent infection or
immune stimulus
Etiology:
1. DM
2. Acute pyelonephritis
3. Chronic Phenacetin use
4. Sickle cell disease

Nephrosclerosis
MC renal disease in essential
hypertension
Hyaline arteriolosclerosis of cortical
arterioles
Tubular atrophy, interstitial fibrosis,
glomerular sclerosis
Small kidneys with a finely granular
cortical surface
Lab: proteinuria, hematuria (no
casts), azotemia

Renal infarction
Causes: emboli from left heart
thrombi, atheroembolic renal
disease, vasculitis
Irregular, wedge-shaped pale
infarctions in cortex
Sudden onset of flank pain and
hematuria

Diffuse cortical necrosis

Complication of obstetric
emergencies and septic shock
Due to DIC limited to renal cortex +
vasospasm
Fibrin clots in arterioles and
glomeruli
Bilateral, diffuse, pale infarct of renal
cortex
Anuria in a pregnant woman followed
by renal failure

Fanconis syndrome
Decreased proximal tubule transport
of amino acids, glucose, phosphate,
uric acid
Can be congenital or acquired
Etiology:
1. Wilsons disease
2. Glycogen storage diseases
3. Cisplatin, expired tetracycline

Features of Fanconis
syndrome
Decreased phosphate reabsorption:
rickets
Decreased bicarbonate reabsorption:
metabolic acidosis, type II RTA
Decreased early Na+ reabsorption:
increased distal Na+ reabsorption,
hypokalemia

Acute renal failure

Abrupt decline in renal function
Increased creatinine and BUN over a
period of several days
1. Prerenal
2. Intrinsic renal
3. Postrenal

Prerenal azotemia
Decreased RBF leads to decreased GFR
Na, H2O and urea are retained by kidney
BUN/creatinine ratio increases to
conserve volume
Urine osmolarity > 500
Urine Na+ < 10
FeNa+ < 1%
Serum BUN/Cr > 20

Intrinsic renal azotemia

Due to acute tubular necrosis, ischemia, toxins

Less commonly due to glomerulonephritis
Patchy necrosis leads to debris
Debris obstruct tubules and there is fluid backflow
across necrotic tubules
GFR decreases, BUN reabsorption is impaired
BUN/creatinine ratio decreases
Urine has epithelial/granular casts
Urine osmolarity < 350
Urine Na+ > 20
FeNa+: > 2%
Serum BUN/Cr < 15

Postrenal azotemia
Outflow obstruction: stones, BPH,
neoplasia, congenital anomalies
Develops only with bilateral
obstruction
Urine osmolarity < 350
Urine Na+ > 40
FeNa+ > 4%
Serum BUN/Cr > 15

Consequences of renal
failure
Inability to make urine and excrete
nitrogenous wastes
Na+ and H2O retention: hypertension,
pulmonary edema, CHF
Hyperkalemia
Metabolic acidosis
Uremia
Anemia
Renal osteodystrophy
Increased triglycerides

Uremia

Increased BUN and creatinine

Nausea and anorexia
Pericarditis
Asterixis
Encephalopathy
Platelet dysfunction

Electrolyte disturbances

Na+
Low: disorientation, stupor, coma
High: irritability, delirium, coma

Cl Low: 2dary to metabolic alkalosis,

hypokalemia, hyperaldosteronism
High: 2dary to non-anion gap
acidosis

K+
Low: U waves on ECG, flattened T
waves, arrhythmias, paralysis
High: peaked T waves, wide QRS,
arrhythmias

Ca++
Low: tetany, neuromuscular
irritability
High: delirium, renal stones,
abdominal pain

Mg++
Low: neuromuscular irritability,
arrhythmias
High: delirium, hyporreflexia,
cardiopulmonary arrest

Phosphate
Low: bone loss, osteomalacia
High: renal stones, metastatic
calcification

Diuretics

Mannitol
Osmotic diuretic
Increases tubular fluid osmolarity, increasing
urine flow
Uses: drug overdose, shock,
intracranial/intraocular hypertension,
rhabdomyolysis
Toxicity:
1. Lung edema
2. Dehydration
3. CI in anuria and CHF

Carbonic anhydrase
inhibitors

Acetazolamide
Site of action: proximal tubule
Mechanism: inhibition of CA
Major effects: increases HCO3- excretion
Uses: glaucoma, urine alkalinization, metabolic
alkalosis, altitude sickness
Toxicity:
1. Hyperchloremic metabolic acidosis
2. Neuropathy
3. NH3 toxicity
4. Sulfa allergy

Loop diuretics
Site of action: thick ascending limb of
loop of Henle
Mechanism: inhibition of Na+, K+,
2Cl- symport
Major effects:
1. Increase Na+, Cl-, K+ and Ca++
excretion
2. Impair ability to concentrate urine
3. Impair ability to dilute urine

Furosemide
Sulfonamide loop diuretic
Increases Ca++ excretion
Uses: edematous states, hypertension,
hypercalcemia
Toxicity:
1. Ototoxicity
2. Hypokalemia, hypocalcemia, hypomagnesemia
3. Dehydration
4. Sulfa allergy
5. Interstitial nephritis
6. Hyperuricemia, gout

Ethacrynic acid
Essentially same action as
furosemide
Not a sulfa drug
Use: diuresis in patients allergic to
sulfa drugs
Toxicity:
1. Similar to furosemide
2. Doesnt cause hyperuricemia

Thiazide diuretics
Site of action: early distal tubule
Mechanism: inhibition of Na+ Clsymport
Major effects:
1. Increase Na+, Cl-, K+ excretion
2. Decrease Ca++ excretion
3. Impair ability to dilute urine (not [])

Hydrochlorothiazide
Uses: hypertension, CHF, idiopathic
hypercalciuria, nephrogenic diabetes
insipidus
Toxicity:
1. Hypokalemic metabolic alkalosis
2. Hyponatremia
3. Hyperglycemia
4. Hyperlipidemia (give indapamide)
5. Hyperuricemia
6. Hypercalcemia
7. Sulfa allergy

K+ sparing diuretics
Site of action: late distal tubule and collecting
duct
Mechanism:
1. Triamterene, amiloride, eplerenone: inhibition
of Na+ reabsorption and K+ secretion in CCT
2. Spironolactone: aldosterone antagonist in CCT
. Major effects:
1. Increase Na+ excretion
2. Decrease K+ excretion
3. Decrease H+ excretion

Uses and toxicity of K+ sparing

diuretics
Uses: hyperaldosteronism, K+
depletion, CHF
Toxicity:
1. Hyperkalemia
2. Arrhythmias
3. Endocrine effects (spironolactone)