GROUP

C2
Physiology Laboratory
Small Group Discussion
Output

March 9, 2016

[ACUTE RENAL FAILURE]

By: ASUBARIO, Olufunmilola Omonike; BALADAD, Alvin Byron; DE JESUS, Chrislou; GURUNG, Man
Bahadur; KALANYEG, Kristie; MAHALEE, Naphitcharak; MONTHATHONG, Thanapol; PANLASIGUI,
Rikkimae Maria; SAMSON, Chino Paolo; SOLONIO, Natalie Keith; VALDEZ, Gregorio
Physiology Laboratory Small Group Discussion Output | Acute Renal Failure 0
 ACUTE RENAL FAILURE

Acute renal failure represents a rapid decline in renal function sufficient to

increase blood levels of nitrogenous wastes and impair fluid and electrolyte balance.
It is a common threat to seriously ill persons in intensive care units, with a mortality
rate ranging from 42% to 88%.1 Although treatment methods such as dialysis and
renal replacement methods are effective in correcting life-threatening fluid and
electrolyte disorders, the mortality rate associated with acute renal failure has not
changed substantially since the 1960s.2,3 This probably is because acute renal
failure is seen more often in older persons than before, and because it frequently is
superimposed on other life-threatening conditions, such as trauma, shock, and
sepsis. The most common indicator of acute renal failure is azotemia, an
accumulation of nitrogenous wastes (urea nitrogen, uric acid, and creatinine) in the
blood. In acute renal failure the glomerular filtration rate (GFR) is decreased. As a
result, excretion of nitrogenous wastes is reduced and fluid and electrolyte balance
cannot be maintained. Persons with acute renal failure often are asymptomatic, and
the condition is diagnosed by observation of elevations in blood urea nitrogen (BUN)
and creatinine.

EPIDEMIOLOGY

The definition of acute renal failure’s (ARF) epidemiology has been, and is
still, limited by the lack of studies evaluating ARF in the community setting, as well
as a lack of comparisons between intensive care unit (ICU) patients and non-ICU
patients. ARF is more common in the ICU and after cardiac surgery.

According to a recently published meta-analysis of 312 studies representing

almost 50 million patients, the pooled incidence and mortality of ARF in hospitalized
adult patients is 21.6% and 23.9%, respectively.

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 Multiple epidemiological studies for acute renal failure have been conducted
in different populations using various criteria and reported a wide range of incidence
and mortality. In several multicenter studies reporting the incidence of renal
replacement therapy requirement in a general intensive care unit population,
however, renal replacement therapy requirement and hospital mortality was quite
similar among the studies, approximately 4% and 60%, respectively. In North and
South America, nephrologists typically manage acute renal failure patients with
intermittent renal replacement therapy. On the other hand, in Asia, Australia and
Europe, intensivists are commonly responsible for managing these patients with
continuous renal replacement therapy.

The incidence of ARF in critically ill patients has increased over the years, as
has the incidence of dialysis-requiring ARF, especially among the elderly, the male
gender, and the black population Overall, mortality has declined for the critically ill,
but the reverse has occurred for ARF patients who need dialysis.

The typical ARF patient is more complex clinically than they were 30 years
ago, and is also more complex than the non-ARF patient; ARF tends to affect people
of older age, who tend to have a higher rate of comorbidities and a greater likelihood
of developing severe disease, multiple organ failure, and sepsis. The leading cause
of ARF is sepsis, followed by nephrotoxin use and ischemia. Septic ARF can be
considered a separate clinical entity from non-septic ARF. Septic ARF patients are
less likely to have pre-existing renal dysfunction and be dependent on dialysis at
discharge, but their disease burden is greater and they are more prone to
concomitant non-renal dysfunction, require mechanically assisted ventilation and
vasoactive drugs, are prone to longer hospital stays, and their probability ofdying is
higher during their stay in hospital. Given the growing incidence of ARF and
consequent increased healthcare burden, measures to prevent ARF have been
sought. Some interventions may help reduce mortality in patients with or at risk of
ARF, such as perioperative hemodynamic optimization, albumin in cirrhotic patients,
spontaneous bacterial peritonitis, and terlipressin for Type 1 hepatorenal syndrome.

In contrast, positive fluid balance, hydroxyethyl starch, and loop diuretics may
have deleterious effects in patients with or at risk of ARF. Unfortunately, prediction of
the risk of ARF is difficult or even impossible in many situations today, which limits
prophylactic action.

CAUSES

Acute kidney failure can occur when:

 You have a condition that slows blood flow to your kidneys

 You experience direct damage to your kidneys

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 Your kidneys' urine drainage tubes (ureters) become blocked and wastes can't
leave your body through your urine

Impaired blood flow to the kidneys

Diseases and conditions that may slow blood flow to the kidneys and lead to kidney
failure include:

 Blood or fluid loss

 Blood pressure medications
 Heart attack
 Heart disease
 Infection
 Liver failure
 Use of aspirin, ibuprofen (Advil, Motrin IB, others), naproxen (Aleve, others) or
related drugs
 Severe allergic reaction (anaphylaxis)
 Severe burns
 Severe dehydration
Damage to the kidneys

These diseases, conditions and agents may damage the kidneys and lead to acute
kidney failure:

 Blood clots in the veins and arteries in and around the kidneys
 Cholesterol deposits that block blood flow in the kidneys
 Glomerulonephritis (gloe-mer-u-loe-nuh-FRY-tis), inflammation of the tiny filters in
the kidneys (glomeruli)
 Hemolytic uremic syndrome, a condition that results from premature destruction
of red blood cells
 Infection
 Lupus, an immune system disorder causing glomerulonephritis
 Medications, such as certain chemotherapy drugs, antibiotics, dyes used during
imaging tests and zoledronic acid (Reclast, Zometa), used to treat osteoporosis
and high blood calcium levels (hypercalcemia)
 Multiple myeloma, a cancer of the plasma cells
 Scleroderma, a group of rare diseases affecting the skin and connective tissues
 Thrombotic thrombocytopenic purpura, a rare blood disorder
 Toxins, such as alcohol, heavy metals and cocaine
 Vasculitis, an inflammation of blood vessels

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Urine blockage in the kidneys

Diseases and conditions that block the passage of urine out of the body (urinary
obstructions) and can lead to acute kidney failure include:

 Bladder cancer
 Blood clots in the urinary tract
 Cervical cancer
 Colon cancer
 Enlarged prostate
 Kidney stones
 Nerve damage involving the nerves that control the bladder
 Prostate cancer

PATHOPHYSIOLOGY

Prerenal Acute Renal Failure

Prerenal ARF, caused by underperfusion of an otherwise normal kidney,

accounted for 21% of cases of ARF in a multicenter study in Madrid. 2 The hallmark
of prerenal failure is that it is quickly reversible with appropriate therapy. Thus, it can
be thought of as “a good kidney looking at a bad world.”

Prerenal kidney failure can be a result of volume depletion from renal or

extrarenal losses, fluid sequestration in liver failure or other edematous states, or

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inadequate perfusion pressure caused by heart failure. The urinalysis is bland and
the urinary sodium level is low, but urine osmolality is high.

Treatment is imperative, because continued renal hypoperfusion can progress

to intrinsic renal failure. Renal perfusion and volume status must be optimized by
giving isotonic fluids. Underlying diseases such as heart failure should be treated.

Postrenal Acute Renal Failure

Postrenal ARF, caused by obstruction of the urinary tract, accounted for 10%
of cases in the Madrid study.2 Urinary tract obstructions may be within the urinary
tract (e.g., blood clots, stones, sloughed papillae, fungus balls), or extrinsic (e.g.,
tumors, retroperitoneal fibrosis, even inadvertent ligation).

Renal ultrasonography, when used to detect obstructions, has a sensitivity

and specificity of 90% to 95%. Unfortunately, it is also highly operator-dependent, so
it should be performed by a highly experienced radiologist. Ultrasonography can
yield false-negative results if the obstruction is caused by retroperitoneal fibrosis or
certain malignancies that encase the entire system. It might also fail to detect an
obstruction in extremely volume-depleted patients who do not have enough fluid
buildup to reveal the obstruction.

Treatment should focus on removing the obstruction. Techniques vary with

the type of obstruction.

Intrinsic Acute Renal Failure

Once prerenal and postrenal causes are ruled out, intrinsic renal failure is
likely. Intrinsic ARF, caused by disease of the renal parenchyma, accounted for 69%
of cases in the Madrid study.2 Acute tubular necrosis (ATN), the most common type
of intrinsic ARF, accounted for 45% of all cases of ARF. Most of the following
discussion is therefore focused on ATN; other types of intrinsic ARF have been
reviewed in detail in studies by Glassock and colleagues.3

ATN is most often caused by renal hypoperfusion and renal ischemia. Other
causes include various endogenous nephrotoxic substances (e.g., myoglobin and
hemoglobin after trauma; cellular products in tumor lysis syndrome; crystals of uric
acid, calcium, or oxalate) and a host of exogenous substances . If a patient develops
ATN while receiving medications, each medication must be reviewed for the
possibility of nephrotoxicity.

In oliguric ATN, renal plasma flow declines, but the glomerular filtration rate
declines even more. This dichotomy suggests that constriction of the afferent
arterioles contributes to the pathophysiologic process. Ischemic injury to epithelial

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cells can lead to tubular back leak, which allows filtrate back into the bloodstream,
and tubular obstruction.

The distribution of tubular necrosis in the kidneys is patchy, and the degree of
necrosis does not correlate with the level of renal dysfunction. This is because the
medulla of the kidneys, containing the thick ascending limbs of Henle, is less well
vascularized and perfused than the cortex and therefore is disproportionately
affected by ischemia. The ischemic insult in this region is worsened by reperfusion
injury. Persistent vasoconstriction and congestion from white cells and cell debris
lead to ongoing hypoxia and necrosis.

The reader may refer to table 1 for a summary.

SIGNS & SYMPTOMS

 Decreased urine output, although occasionally urine output remains normal

 Fluid retention, causing swelling in your legs, ankles or feet
 Drowsiness
 Shortness of breath
 Fatigue
 Confusion
 Nausea
 Seizures or coma in severe cases
 Chest pain or pressure

DIAGNOSIS

 Blood tests. Kidney function tests look for the level of waste products, such
as creatinine and urea, in your blood.
 Urine tests. Analyzing a sample of your urine may reveal abnormalities that
point to chronic kidney failure and help identify the cause of chronic kidney
disease.
 Imaging tests. Your doctor may use ultrasound to assess your kidneys'
structure and size. Other imaging tests may be used in some cases.
 Removing a sample of kidney tissue for testing. Your doctor may
recommend a kidney biopsy to remove a sample of kidney tissue. Kidney
biopsy is often done with local anesthesia using a long, thin needle that's
inserted through your skin and into your kidney. The biopsy sample is sent to
a lab for testing to help determine what's causing your kidney problem.

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 Renal failure

Sodium and water Potassium Elimination of Erythropoietin Acid-base Activation of Phosphate

balance balance nitrogenous production balance vitamin D elimination
wastes

Hypertension Hyperkalemia Anemia Skeletal

buffering
Hypocalcemia

Coagulopathies
Increased

vascular Edema
volume Acidosis
Uremia
Hyperparathyroidism

Heart
Pericarditis
failure

Skin Gastrointestinal Neurologic Sexual

disorders manifestations manifestations dysfunction
Osteodystrophies

Table 1

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TREATMENT AND MANAGEMENT OF ACUTE RENAL FAILURE

Treatment for acute kidney failure typically requires a hospital stay. Most
people with acute kidney failure are already hospitalized. How long you'll stay in the
hospital depends on the reason for your acute kidney failure and how quickly your
kidneys recover.

In some cases, you may be able to recover at home.

Treating the underlying cause of your kidney failure

Treatment for acute kidney failure involves identifying the illness or injury that
originally damaged your kidneys. Your treatment options depend on what's causing
your kidney failure.Treating complications until your kidneys recover

Your doctor will also work to prevent complications and allow your kidneys time to
heal. Treatments that help prevent complications include:

 Treatments to balance the amount of fluids in your blood.If your acute

kidney failure is caused by a lack of fluids in your blood, your doctor may
recommend intravenous (IV) fluids. In other cases, acute kidney failure may
cause you to have too much fluid, leading to swelling in your arms and legs. In
these cases, your doctor may recommend medications (diuretics) to cause
your body to expel extra fluids.
 Medications to control blood potassium. If your kidneys aren't properly
filtering potassium from your blood, your doctor may prescribe calcium,
glucose or sodium polystyrene sulfonate (Kayexalate, Kionex) to prevent the
accumulation of high levels of potassium in your blood. Too much potassium
in the blood can cause dangerous irregular heartbeats (arrhythmias) and
muscle weakness.
 Medications to restore blood calcium levels. If the levels of calcium in your
blood drop too low, your doctor may recommend an infusion of calcium.
 Dialysis to remove toxins from your blood. If toxins build up in your blood,
you may need temporary hemodialysis — often referred to simply as dialysis
— to help remove toxins and excess fluids from your body while your kidneys
heal. Dialysis may also help remove excess potassium from your body.
During dialysis, a machine pumps blood out of your body through an artificial
kidney (dialyzer) that filters out waste. The blood is then returned to your
body.

Lifestyle and home remedies

 Choose lower potassium foods. Your dietitian may recommend that you
choose lower potassium foods. High-potassium foods include bananas,

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 oranges, potatoes, spinach and tomatoes. Examples of low-potassium foods
include apples, cabbage, green beans, grapes and strawberries.
 Avoid products with added salt. Lower the amount of sodium you eat each
day by avoiding products with added salt, including many convenience foods,
such as frozen dinners, canned soups and fast foods. Other foods with added
salt include salty snack foods, canned vegetables, and processed meats and
cheeses.
 Limit phosphorus. Phosphorus is a mineral found in foods, such as milk,
cheese, dried beans, nuts and peanut butter. Too much phosphorus in your
blood can weaken your bones and cause skin itchiness. Your dietitian can
give you specific recommendations on phosphorus and how to limit it in your
particular situation.
 As your kidneys recover, you may no longer need to eat a special diet,
although healthy eating remains important.

Prevention

 Pay attention to labels when taking over-the-counter (OTC) pain

medications. Follow the instructions for OTC pain medications, such as
aspirin, acetaminophen (Tylenol, others) and ibuprofen (Advil, Motrin IB,
others). Taking too much of these medications may increase your risk of
acute kidney failure. This is especially true if you have pre-existing kidney
disease, diabetes or high blood pressure.
 Work with your doctor to manage kidney problems. If you have kidney
disease or another condition that increases your risk of acute kidney failure,
such as diabetes or high blood pressure, stay on track with treatment goals
and follow your doctor's recommendations to manage your condition.
 Make a healthy lifestyle a priority. Be active; eat a sensible, balanced diet;
and drink alcohol only in moderation — if at all.

References:

1. Guyton, AC; Hall, JE: Textbook of Medical Physiology, 11 th edition. Elsevier

Inc. 2006.

2. Koeppen, BM; Stanton, BA: Berne and Levy Physiology, 6 th edition. Elsevier
Inc. 2010.

3. en.wikipedia.org

4.http://www.mayoclinic.org/diseases-conditions/kidneyfailure/basics/prevention/
con-20024029
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