ANATOMY PHYSIOLOGY

1. Acute Renal Failure

2. To function properly
kidneys require
• Normal renal blood flow
• Functioning glomerulus and
tubules
• Clear urine outflow tract: to
eliminate formed urine

3. Azotemia: elevated blood urea
nitrogen not from an intrinsic renal
disease
Oliguria: urine output less
than 500cc/24hr.
Nonoliguria: urine output greater
than 500cc/24hr.
Anuria: urine output less than
50cc/24hr.

4. Renal auto regulation
• It is the maintenance of near normal
intrarenal hemodynamic environment
despite large changes in the
systemic blood pressure

5. Renal auto regulation
• RBF (Renal Blood Flow): 1200ml/min
• RPF(Renal Plasma Flow):670ml/min I.e
60-70%of RBF
• GFR: 125ml/min
• FF(Filtration fraction):ratio of
GFR:RBF
(Normal : 0.18-0.21)

6. Renal auto regulation
• F = ΔP
R
F= flow RAP=Renal arterial pressure
ΔP= pressure changes Raff=afferent art. resistance
R= resistance Reff=efferent art. resistance
RBF~ RAP
Raff+Reff

7. Introduction
• Acute renal failure (ARF) is the
rapid breakdown of renal (kidney)
function
• It occurs when high levels of uremic
toxins accumulate in the blood.
• ARF occurs when the kidneys are
unable to excrete the daily load of
toxins in the urine.

8. Definition
Acute renal failure (ARF), also known
as acute kidney failure or acute
kidney injury, is a rapid loss of renal
function due to damage to the
kidneys, resulting in retention of
nitrogenous (urea and creatinine) and
non-nitrogenous waste products that
are normally excreted by the kidney.

9. Acute renal failure is a
syndrome defined by a sudden
loss of renal function over
several hours to several days.

10. What constitutes the ARF?
• Accumulation of nitrogenous waste
products.
• Increased S cr.
• Derangement of extracellular fluid
balance.
• Acid-base disturbance.
• Electrolyte and mineral disorders.

11. Acute Renal Failure
• Sudden decrease in function (hours-
days)
• Often multifactorial
• oliguric < 400 ml
• Non-oliguric (up to 65%)
• Associated with high mortality and
morbidity

12. Types
Renal Failure is categorized according
to the causes as:
 Pre-renal
 Intrinsic
 Post-renal

16. Pre-renal
1. Hypovolemia (ECF volume depletion)
• shock
• dehydration
• hepatorenal syndrome
• severe burns
• Excessive diuresis,
• hemorrhage,
• GI losses,
• loss of intravascular fluid into the extravascular
space

17. 2 Low cardiac output
• Cardiomyopathy,
• MI
• cardiac tamponade
• pulmonary embolism
• pulmonary hypertension
• positive-pressure mechanical ventilation
3. Low systemic vascular resistance
• Septic shock
• liver failure
• antihypertensive drugs

18. 4. Increased renal vascular resistance
• NSAIDs
• hypercalcemia,
• anaphylaxis,
• anesthetics,
• renal artery obstruction,
• renal vein thrombosis,
• sepsis,
• hepatorenal syndrome
5. Decreased efferent arteriolar tone
• ACE inhibitors or angiotensin II receptor
blockers

19. Intrinsic …
1 Acute tubular injury
• Ischemia
• Surgery
• hemorrhage
• arterial or venous obstruction,
• Toxins or medication (e.g. some NSAIDs,
aminoglycoside antibiotics, iodinated
contrast,
• rhabdomyolysis
• hemolysis
• multiple myeloma

20. Contd.
2 acute glomerulonephritis
3. Infiltrative diseases
– Lymphoma,
– sarcoidosis,
– leukemia

21. Post-renal
1 Tubular precipitation
• Uric acid (tumor lysis), sulfonamides
2 Ureteral obstruction
• Intrinsic: Calculi, clots, sloughed renal
tissue, fungus ball, edema, malignancy,
congenital defects
• Extrinsic: Malignancy, retroperitoneal
fibrosis, ureteral trauma during
surgery or high impact injury

22. 3 Bladder obstruction
– Mechanical:
• Benign prostatic hyperplasia,
• prostate cancer,
• bladder cancer,
• urethral strictures,
• Phimosis/paraphimosis,
• urethral valves, obstructed indwelling
urinary catheter
– Neurogenic:
• Anticholinergic drugs,
• upper or lower motor neuron lesion

23. The Pathophysiology of ARF
ARF
Prerenal Postrenal
Intrarenal
Vascular Interstitial
Tubular
Glomerular
Ischemia
Pigments
Toxins
JASN 1998;9(4):710-718

24. Pathophysiology I
Causes
Damage of tubules
Unable to conserve sodium normally
Reactivation of renin-angiotension-aldosterone system
Increases the tone of afferent and efferent arterioles
Redistributes the renal vascular supply
Results in ischemia
Increase in vasopressin

25. cellular swelling
-inhibition of prostaglandin synthesis
Further stimulation of R-A-S
Reduced blood flow
Decreased glomerular pressure
Decreased GFR/ tubular flow
oliguria

26. Pathophysiology II
cellular/protein debris within the tubule
obstructs lumen
Raises intratubular pressure
Increases oncotic pressure
Opposes the filtration pressure
Decreased GFR
Oliguria
Renal failure

27. Pathophysiology III : Biochemical theory
Prerenal causes
Decreased renal blood flow
Reduced oxygen to tubules
Decrease in cellular ATP
Increases cytosolic and mitochondrial calcium conc.
Inability of kidneys to function
Decreased GFR
Oliguria
Renal failure

28. Urine output
• Prerenal causes typically present
with oliguria, not anuria.
• A relatively preserved urine output
of 1 to 2.4 L/day is initially
present in most renal causes.
•

29. In acute tubular injury, output may
have 3 phases.
• Oliguric phase/non oliguric phase
• Diuretic phase
• Recovery phase

30. 1 Oliguric/non oliguric phase
• The oliguric phase, with output
typically between 50 and 400
mL/day, lasts an average of 10 to 14
days but varies from 1 day to 8 wk.
• However, many patients are never
oliguric. Nonoliguric patients have
lower mortality and morbidity and
less need for dialysis.

31. 2. Diuretic phase
• Gradual/abrupt return to GF and
leveling BUN
• Diuretic phase
• Urine output 1000-2000ml/day
• Dehydration

32. 3. Recovery phase
• In the recovery phase, urine output
gradually returns to normal, but
serum creatinine and urea levels may
not fall for several more days.

33. Symptoms and Signs
• weight gain
• peripheral edema
• Azotemia
• anorexia,
• nausea and vomiting,
• weakness,
• myoclonic jerks,
• seizures,
• confusion,
• coma; asterixis and hyperreflexia may be
present on examination.

34. • Chest pain
• cola-colored urine
• Decreased urine output/frequency of urination
• Breathlessness
• Cough
• Fluid retention
• Hypertension
• Nausea
• Vomiting
• Diarrhoea
• Malaise
• Tachycardia
• Cardiac arrythmias
• Dehydration
• Tachycardia

35. Stepwise Diagnostic Approach
to Acute Renal Failure
• Step 1
– History
– Record review
– Physical examination
• Volume status assessment
– Bladder evaluation
– Urinalysis

36. Stepwise Diagnostic Approach to
Acute Renal Failure
• Step 2
– Urinary indices
– Renal/urinary imaging
– Additional volume status measures
– Renal vascular status
– Blood and urine lab tests

37. Stepwise Diagnostic Approach to
Acute Renal Failure
• Step 3
– Consider therapeutic trials
• Volume challenge
• Foley placement
• Hemodynamic support
• Step 4
– Consider renal biopsy

38. History
• A detailed and accurate history is crucial to aid
in diagnosing the type of ARF and in
determining its subsequent treatment.
• A detailed history
• physical examination
• routine laboratory tests
are useful in making a correct diagnosis

39. History
• A history of chronic symptoms of
• fatigue,
• weight loss,
• anorexia,
• nocturia,
• pruritus
Exposure to heavy metals

40. Past medical history:
Hypertension
Congestive cardiac failure
Diabetes
Multiple myeloma
Chronic infection
Myeloproliferative disorder

41. Physical Examination
• Hypotension
Volume contraction
Congestive heart failure
Nephrotoxic drug ingestion
History of trauma or unaccustomed exertion
Blood loss or transfusions
Evidence of connective tissue disorders or
autoimmune diseases
Exposure to toxic substances, such as ethyl
alcohol or ethylene glycol
Urine output history can be useful.

42. • Skin
Examination of the skin for petechiae, purpura,
ecchymosis, and livedo reticularis provides
clues to inflammatory and vascular causes of
ARF
• Eyes
Evidence of uveitis may indicate
interstitial nephritis and necrotizing
vasculitis.
Ocular palsy may indicate ethylene glycol
poisoning or necrotizing vasculitis.

43. Contd…
Cardiovascular system
hypertension, atheroembolic disease, and
endocarditis may be observed after a
careful examination of the eyes.
• Cardiovascular system
The most important part of the physical
examination is the assessment of
cardiovascular and volume status.
The physical examination must include
pulse rate and blood pressure recordings
measured in both the supine position and
the standing

44. Contd…
position; close inspection of the
jugular venous pulse; careful
examination of the heart, lungs,
skin turgor, and mucous membranes;
and assessment for the presence of
peripheral edema.
Accurate daily records of fluid
intake and urine output and daily
measurements of patient weight are
important.
Blood pressure recordings can be
important diagnostic tools.

45. Contd…
perfusion is poor, which can result in
AKI.
Severe hypertension with renal failure
suggests renovascular disease,
glomerulonephritis, vasculitis, or
atheroembolic disease.
Abdominal examination findings can be
useful Hypovolemia leads to hypotension;
however, hypotension may not necessarily
indicate hypovolemia.

46. Contd….
• Severe congestive cardiac failure
(CHF) may also cause hypotension.
Although patients with CHF may
have low blood pressure, volume
expansion is present and effective
renal to help detect obstruction at
the bladder outlet as the cause of
renal failure, which may be due to
cancer or an enlarged prostate
The presence of an epigastric bruit suggests renal
vascular hypertension

47. Effects of ARF
 Fluid-electrolyte imbalance
 Fluid overload/depletion
 Hyperkalemia
 Hyponatremia
 Hypocalcaemia
 Hypermagnesaemia
 Acidosis
 Hamatopoietic
 Increased susceptibility to infection
 Anemia
 Platelet dysfunction
 GI complications
 Anorexia
 Nausea
 Vomiting
 Diarrhea
 Constipation
 stomatitis

48. Contd…
 Cardiovascular
 Arrhythmia
 Pericardial friction rub
 Hyperkalemia
 Metabolic acidosis
 HTN
 Increased JVP
 Edema
 Increased incidence of pericarditis
 Uremic encephalopathy
 Apathy
 Defective recent memory
 Dysarthria
 Tremors
 Convulsions
 coma

49. Contd…
 Impaired wound healing
 Respiratory
 Altered ABG
 Rates
 Effusions
 Kausmaul’s respirations

50. diagnosis
• In general, renal failure is diagnosed when either
creatinine or blood urea nitrogen tests are
markedly elevated in an ill patient, especially when
oliguria is present. Previous measurements of renal
function may offer comparison, which is especially
important if a patient is known to have chronic
renal failure as well. If the cause is not apparent,
a large amount of blood tests and examination of a
urine specimen is typically performed to elucidate
the cause of acute renal failure, medical
ultrasonography of the renal tract is essential to
rule out obstruction of the urinary tract.
• Consensus criteria (RIFLE)[1][2] for the diagnosis
of ARF are:
• Risk: serum creatinine increased 1.5 times OR
urine production of <0.5 ml/kg body weight for 6
hours

51. contd
• Injury: creatinine 2.0 times OR urine production
<0.5 ml/kg for 12 h
• Failure: creatinine 3.0 times OR creatinine >355
μmol/l (with a rise of >44) or urine output below
0.3 ml/kg for 24 h
• Loss: persistent ARF or complete loss of kidney
function for more than four weeks
• End-stage Renal Disease: complete loss of kidney
function for more than three months
• Kidney biopsy may be performed in the setting of
acute renal failure, to provide a definitive
diagnosis and sometimes an idea of the prognosis,
unless the cause is clear and appropriate screening
investigations are reassuringly negative.

53. Treatment
• Acute renal failure may be reversible if treated
promptly and appropriately. Resuscitation to
normotension and a normal cardiac output is key.
The main interventions are monitoring fluid intake
and output as closely as possible; insertion of a
urinary catheter is useful for monitoring urine
output as well as relieving possible bladder outlet
obstruction, such as with an enlarged prostate. In
the absence of fluid overload, administering
intravenous fluids is typically the first step to
improve renal function. Fluid administration may
be monitored with the use of a central venous
catheter to avoid over- or under-replacement of
fluid. If the cause is obstruction of the urinary
tract, relief of the obstruction (with a
nephrostomy or urinary catheter) may be
necessary

54. • Metabolic acidosis and hyperkalemia, the two most
serious biochemical manifestations of acute renal
failure, may require medical treatment with
sodium bicarbonate administration and
antihyperkalemic measures, unless dialysis is
required.
• Should hypotension prove a persistent problem in
the fluid replete patient, inotropes such as
norepinephrine and/or dobutamine may be given to
improve cardiac output and hence renal perfusion.
While a useful pressor, there is no evidence to
suggest that dopamine is of any specific benefit,[3]
and at least a suggestion of possible harm. A
Swan-Ganz catheter may be used, to measure
pulmonary artery occlusion pressure to provide a
guide to left atrial pressure (and thus left heart
function) as a target for inotropic support.

55. • The use of diuretics such as furosemide, while
widespread and sometimes convenient in
ameliorating fluid overload, does not reduce the
risk of complications and death.[4] In practice,
diuretics may simply mask things, making it more
difficult to judge the adequacy of resuscitation.
• The use of an ACE Inhibitor (such as benazepril)
can help protect renal function in patients with
advanced renal insufficiency. [5] However, an
increase of up to 30% in SCr (serum creatinine) is
expected. This is because the ACEI reduces
Angiotensin II levels. Angiotensin II causes renal
efferent arteriole vasoconstriction, and reduction
of angiotensin II leads to vasodialation which in
turn reduces GFR. This reduction in GFR causes
the predicted increase in SCr.

56. • However, one must not use a NSAID as NSAIDs
reduce prostaglandin production. Prostaglandins
cause vasodialation of the renal afferent
arteriole, and a reduction in prostaglandin leads to
vasoconstriction thus reducing GFR. However, this
can lead to nephrotoxicity and thus NSAIDs must
be avoided. [6]
• Lack of improvement with fluid resuscitation,
therapy-resistant hyperkalemia, metabolic
acidosis, or fluid overload may necessitate
artificial support in the form of dialysis or
hemofiltration. Depending on the cause, a
proportion of patients will never regain full renal
function, thus having end stage renal failure
requiring lifelong dialysis or a kidney transplant

58. Predictors of Dialysis in
ARF
• Oliguria:
– <400cc/24hr 85% will require dialysis
– >400cc/24hr 30-40% will require dialysis
• Mechanical ventilation
• Acute myocardial infarction
• Arrhythmia
• Hypoalbuminemia
• ICU stay
• Multi-system organ failure
JASN 9(4):692-698, 1998 Arch IM 160:1309-1313, 2000

59. Contd..

60. Treatment of ARF
• Eliminate the toxic insult
• Hemodynamic support
• Respiratory support
• Fluid management
• Electrolyte management
• Medication dose adjustment
• Dialysis

61. Prevention of ARF
• Diminish risk of nosocomial infection
– conservative use of IV catheters
– judicious use of antibiotics
– hand-washing
• Prevention of nephrotoxicity
– avoid/reduce nephrotoxins
– IV NS
– N-acetylcysteine, sodium bicarbonate
– correct hypokalemia, hypomagnesemia
– correct/treat other systemic diseases
• Pharmacology
– avoid overlapping nephrotoxins
– follow drug levels closely
• Attention to fluid status
– Regular weights, I & O
JASN 9(4):710-718, 1998