er conference co* concepcion * conti * corpuz * cosico * cruz * cruz

ER CONFERENCECo* Concepcion * Conti * Corpuz * Cosico * Cruz * Cruz

General Data

10-month-old, Female From Isabela

Chief Complaint: Pallor and anuria for 2

days

8 days

PTALoose, blood-streaked, mucoid, greenish stools

4-5 x per day ~1 cup per episode

Associated with vomiting of previously ingested milkGood urine outputBrought to a private doctor

Advised ORS after each bowel movement

Metronidazole 30mg/kg/day

History of Present Illness

3 days

PTA 1 episode of bowel movement

Non-blood streaked, formed stools

no vomiting

Decrease in urine output

Highly colored urine

History of present Illness

1 day

PTA 5 episodes of vomiting

Pallor

No urine output

Brought back to private doctor

Referred to USTH for further

management

History of Present Illness

TRANSFER TO USTH

Family History

(-) kidney disease

Physical Examination

Irritable but not in respiratory distress Vital signs were as follows:

BP 90/60 mmHg Anthropometric measurements :

Lt : 75 cm (p75) Wt : 10 kg (p75) Pale, dry skin and petechial rash on the abdomen Anterior fontanel and eyeballs slightly sunken Liver – palpable 3 cm below RSCM Liver span 6cm Urinary bladder not palpable Strong peripheral pulses No signs of edema

Other pertinent information

blahblah

Approach to Diagnosis

Salient Features

10 mo old/F Diarrhea Vomiting Anuria Pallor

Signs of dehydration Slightly sunken

fontanelles and eyeballs

Irritability Dry skin

Petechial rash Hepatomegaly? Strong pulses

Subjective Objective

Presenting Manifestation

Look for a symptom, sign or laboratory finding.. Pathognomonic of a disease Pointing to an organ or part of an organ Pointing to a group of disease Mechanism is well understood Found in the least number of diseases

UST: Pedia (2009). Guideline for History Taking, PE and Diagnosis of Pediatric Patients. 2nd ed.

Presenting Manifestation

Look for a symptom, sign or laboratory finding.. Pathognomonic of a disease Pointing to an organ or part of an organ Pointing to a group of disease Mechanism is well understood Found in the least number of diseases

UST: Pedia (2009). Guideline for History Taking, PE and Diagnosis of Pediatric Patients. 2nd ed.

“GI: Vomiting and diarrhea and w/ signs of dehydration

Renal: anuriaPetechial rash”

Differential Diagnosis

HSP HUS Acute gastroenteritis

Epidemiology Primary childrens’ disease (3-15 y/o)

Affects children under 5

Older children >5 years old

Pathogenesis immune-mediated vasculitis associated with IgA deposition

Ingestion of contaminated foodstuff E-coli producing Shiga-toxin

Campylobacter, Salmonella, Shigella, E. coli, E histolitica inflammation of intestines

Clin Manifestation

-Palpable purpura w/o thrombocytopenia and coagulopathy -Arthritis/arthralgia -Abdominal pain -Renal disease

prodromal illness: abdominal pain, vomiting, and diarrheaSudden onset of:Hemolytic anemia with fragmented erythrocytes Thrombocytopenia Acute renal injury

FeverDiarrhea with blood or mucusVomitingAbdominal pain+/- signs of dehydration

IMPRESSION:HEMOLYTIC UREMIC SYNDROME

Hemolytic uremic syndrome (HUS) One of the main causes of AKI in children

under 3 years of age and an important cause of chronic renal failure and shock during youth

Classical triad: Microangiopathic hemolytic anemia Thrombocytopenia Acute kidney injury

Niaudet, Patrick (2009). Clinical Manifestation and diagnosis of Shiga-like toxin associated (typical) Hemolytic Uremic Syndrome in children.

Uptodate 17.1 desktop

Hemolytic uremic syndrome (HUS) 90% of cases are preceded by a

prodrome of bloody diarrhea toxin-mediated endothelial cell damage,

resulting in thrombotic microangiopathy and intraluminal thrombosis of small vessels, with subsequent tissue ischemia and necrosis



Shiga-like toxin associated HUS (90%) Aka typical, classical, or diarrhea-

associated HUS Escherichia coli and type 1 Shigella

dysenteriae Enterohemorrhagic E. coli (EHEC) produces a

toxin called verotoxin and accounts for 70% of post-diarrheal HUS

80% of EHEC are caused by E. coli O157:H7 Shigella dysenteriae type 1: more severe HUS



Types of HUS

Types of HUS

Non-shiga-like toxin associated HUS (10%) aka atypical, nondiarrhea-associated HUS absence of diarrhea or Shiga toxin-

producing E. coli infection Most commonly due to Strep pneumoniae Prodromal features of URTI, fever or

vomiting



Clinical Manifestation

Prodromal illness with abdominal pain, vomiting and diarrhea immediately precedes HUS Prodromal diarrhea was present in 91%

Diarrhea was bloody in 57% of cases Vomiting occurs in 30 to 60% of cases Fever occurs in 30%.

HUS begins 5-10 days after the onset of diarrhea. There is sudden onset of: Anemia (microangiopathic hemolytic anemia) Thrombocytopenia Acute Renal injury

Clinical Manifestation

• Early symptoms:– Blood in the stools – Irritability – Fever – Lethargy and Weakness– Vomiting and diarrhea

• Later symptoms– Bruising/Skin rash that looks like fine red spots (petechiae) – Jaundice– Decreased consciousness – Oliguria/Anuria– Pallor – Seizures

http://www.niddk.nih.gov/

Clinical Course



Pathogenesis

Pathogenesis

The primary event in pathogenesis of the syndrome appears to be endothelial cell injury.

Capillary and arteriolar endothelial injury in the kidneys leads to localized clotting.

The microangiopathic anemia results from mechanical damage to the red blood cells as they pass to the altered vasculature.

Thrombocytopenia is due to intrarenal platelet adhesion or damage.

Summary of the Pathophysiology

Ingestion of EHEC containing shiga toxin

Attaches to endothelial lining

Circulatory system

RBC WBCPlatelet

Apoptosis

Hemolysis

Hemolytic anemia

Pallor

Highly colored urine

Platelet aggregation

Damage Inflammation

CytokinesTNF aIL-8

Microthrombi

Consumptive thrombocytopen

ia

PetechiaeDeposited in various

organs particularly Kidney

Microangiopathic hemolytic anemia

Microangiopathic hemolytic anemia endothelial cell injury leading to

intravascular coagulation, fibrin deposition, and platelet adherence to microthrombi within the vascular lumen Altered blood flow results in red blood cell destruction.

Low hemoglobin Negative coomb’s test Peripheral blood smear

schistocytes (up to 10 percent of red cells)Tzipori S, Sheoran A, Akiyoshi D, Donohue-Rolfe A, and Trachtman H. Antibody Therapy in the Management of Shiga Toxin-Induced Hemolytic Uremic Syndrome. Clinical Micro

Reviews, 2004 V17 No4, p. 926–941

Thrombocytopenia

Thrombocytopenia

platelet count below 140,000/mm3 and usually about 40,000/mm3.

Despite this, there is usually no purpura or active bleeding



Acute Renal Injury

Acute Kidney Injury

clinical syndrome in which a sudden deterioration in renal function results in the inability of the kidneys to maintain fluid and electrolyte homeostasis

Present in 55-70% of HUS renal function recovers in most of them

(up to 70% in various series)

Rifle Criteria

Barlettaa, G.M.& Bunchman T.E. Acute renal failure in children and infants. Curr Opin Crit Care 10:499–504., 2004

Etiology of Acute Renal Failure

Biljon, GV. Causes, Prognostic Factors and Treatment Results of Acute Renal Failure in Children Treated in a Tertiary Hospital in South Africa. Journal of Tropical Pediatrics Vol.

54, No. 4, 13 March 2008

Urinalysis, Urine Chemistries, and Osmolality in Acute Renal Failure

HYPOVOLEMIAACUTE TUBULAR NECROSIS

ACUTE INTERSTITIAL NEPHRITIS

GLOMERULONEPHRITIS OBSTRUCTION

Sediment Bland Broad, brownish granular casts

White blood cells, eosinophils, cellular casts

Red blood cells, red blood cell casts Bland or bloody

Protein None or low None or lowMinimal but may be increased with NSAIDs

Increased, >100 mg/dL Low

Urine sodium, mEq/L[*] <20 >30 >30 <20 <20 (acute)

>40 (few days)

Urine osmolality, mOsm/kg >400 <350 <350 >400 <350

FE Na <1 >1 Varies <1 <1 (acute) >1 (few days)

Kliegman: Nelson Textbook of Pediatrics, 18th ed.

Complications of AKI

Hyponatremia Most common cause is accumulation of fluid in

excess of solute Hyperkalemia

Result of the inability to excrete quantitatively the potassium derived from the diet, as well as that released from catabolism, necrotic tissue, and hemolyzed erythrocytes

Hypocalcemia &Hyperphosphatemia Almost constant early finding in ARF Due to phosphate retention, coupled with release

of phosphate from tissue breakdown, contribute to the depression of the serum calcium concentration



Metabolic Acidosis May occur via 3 basic mechanisms:

Loss of bicarbonate from the body Impaired ability to excrete acid by the kidney Addition of acid to the body (exogenous or

endogenous)



Hypertension May result from hyperreninemia associated

with the primary disease process and/or expansion of the extracellular fluid volume and is most common in ARF patients with acute glomerulonephritis or HUS



Uremia Accumulation of nitrogenous wastes w/c are

normally excreted in the urine Occurs in GFR <50% Early symptoms: anorexia and lethargy Late symptoms: decreased mental acuity

and coma

Other Systems Involved

Other Systems involved

Central nervous system (20%): seizures, coma, stroke, hemiparesis, and cortical blindness. Severe CNS involvement is associated with increased mortality.

Gastrointestinal tract: Any area from the esophagus to the perianal area can be involved. The more serious manifestations include severe hemorrhagic colitis, bowel necrosis and perforation, rectal prolapse, peritonitis, and intussusception.

Cardiac dysfunction: Cardiac dysfunction can be due to cardiac ischemia detected by elevated levels of troponin I, uremia, and fluid overload.

Other Systems involved

Pancreas: transient diabetes mellitus may occur, and rarely permanent diabetes mellitus, which may develop years later.

Liver: Hepatomegaly and/or increased serum transaminases are frequent findings.

Hematology: In addition to anemia and thrombocytopenia, leukocytosis is common in diarrhea-induced HUS; the prognosis is worse with increased white blood cell counts

Diagnostics

Diagnosis

Based on presenting signs and symptoms. The classic diagnostic criteria:

microangiopathic hemolytic anemia thrombocytopenia acute renal failureFollowed by an episode of bloody diarrhea

• Physical Examination may show:– Hepatomegaly/ Splenomegaly– Neurologic changes

Diagnosis

• Laboratory tests:– Blood clotting tests (PT and PTT) – BUN and creatinine – Complete blood count – Platelet count – Urinalysis– Urine protein

• Other tests: – Kidney biopsy – Stool culture

McMillan R. Hemorrhagic disorders: abnormalities of platelet and vascular function. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 179.

What labs can we request for our patient

CBC with platelet count Reticulocyte count Peripheral smear Urinalysis PT, aPTT Serum electrolytes Creatinine Blood culture Stool culture


CBC with platelet count Hemoglobin=5-9 g/dL White blood cell count may rise to

30.000/mm3 Magnitude related to severity and prognosis of

the syndrome Thrombocytopenia (20.000 - 100.000/mm3)

occurs in more than 90% of patients.


Reticulocyte count Reticulocyte count is moderately elevated


Peripheral smear Helmet cells, burr cells and fragmented red

blood cells


Urinalysis microscopic hematuria and proteinuria


PT, aPTT Usually within normal range however may

also show prolonged bleeding time.


Serum electrolytes Hyperkalemia Hyperphosphatemia Hypocalcemia Metabolic acidosis


BUN, Creatinine Markedly elevated BUN and creatinine


Stool culture Typically detect shiga toxin-producing E coli

Blood culture Negative

Treatment

Treatment

Current treatment of STEC induced HUS targets gastrointestinal, hematologic, vascular and renal complications. It includes isotonic volume replacement or

expansion, red blood cell and platelet transfusion and, for severe AKI, hemo- or peritoneal dialysis

Nelson’s Textbook of Pediatrics, 18th edition

Kidney International (2009) 75, S62–S66; doi:10.1038/ki.2008.624Treatment options for HUS secondary to Escherichia coli O157:H7

1Division of Nephrology, Montreal Children's Hospital and McGill University, Montreal, Quebec, CanadaCorrespondence: Martin Bitzan, Division of Nephrology, Montreal Children's Hospital, 2300, rue Tupper –

E222, Montreal, Quebec, Canada H3H 1P3.

Treatment

Supportive care with meticulous attention to Anemia Thrombocytopenia AKI and complications

Fluid and electrolytes Hypertension Uremia

Wong CS, Jelacic S, Habeeb RL, Watkins SL, Tarr PI: The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med 342 : 1930 –1936, 2000

Bihar Pedicon 2006 - Conference Abstracts.Pediatric Oncall [serial online] 2006 [cited 15 September 2006(Supplement 9)];3.

Anemia

packed red blood cells (RBC) should be transfused when the hemoglobin (Hgb) level is <7 g/dL or hematocrit <18

About 80 percent of patients w/ HUS require PRBC transfusions

guidelines for children >4 months of age are similar to those used in adults. In general, RBC transfusion is recommended for Hgb levels <7 g/dL, since most such children become symptomatic with malaise, irritability, and/or lassitude

Teruya, Jun (2009). Indications for RBC transfusion in infants and children. Uptodate 17.1 Desktop

Thrombocytopenia

Platelet transfusion is reserved for patients with HUS who have significant clinical bleeding or if an invasive procedure is required.

Rare bec platelet count rarely <10,000/mm3

based upon unsubstantiated concerns that consumption of infused platelets would contribute to new or expanding thrombi as reported in adults with thrombotic thrombocytopenic purpura



Fluids

Fluid management is based upon the intravascular fluid status of the patient and renal function. Decreased intravascular volume are repleted

to an euvolemic state. Increased volume and diminished urine

output are fluid restricted. Diuretics rarely avert anuria but a trial of

furosemide (2 to 5 mg/kg per dose) may be attempted to induce a diuresis

Dialysis therapy is required if fluid restriction and/or diuretic therapy fail



Fluids

Once the patient is in an euvolemic state, administration of fluids should be given as insensible losses plus urine output until renal function returns to normal



Electrolytes

Common due to acute kidney injury/failure Hyperkalemia Hyperphosphatemia Metabolic acidosis



Electrolytes

Hyperkalemia Stabilization of the cardiac membrane with the intravenous

calcium (calcium gluconate 10 percent solution in a dose 0.5 to 1.0 mL per kilogram intravenously over 5 to 15 minutes).

Promotion of potassium movement from the extracellular fluid (ECF) into the cells via three different therapies: Glucose and insulin (0.5 to 1.0 g of glucose per kilogram over 30

minutes and 0.1 unit of insulin per kilogram intravenously or subcutaneously);

intravenous sodium bicarbonate (in a dose of 1 to 2 milliequivalent per kilogram over 30 to 60 minutes);

beta agonists, such as albuterol, via nebulization (2.5 mg if the child weighs less than 25 kilogram or 5 mg if the child weighs more).



Electrolytes

Hyperphosphatemia and hypocalcemia Oral phosphate binders and dietary

restriction of phosphorus are commonly used to decrease intestinal absorption of phosphorus.

Intravenous administration of calcium gluconate should be considered if hypocalcemia is severe and/or if bicarbonate therapy is required for severe acidosis and hyperkalemia



Electrolytes

Acidosis Due to inability to excrete acid. Patients with serum bicarbonate levels that

are above 14 mEq/L or with arterial pH greater than 7.2 do not require intervention.



Dialysis

2/3 of HUS patients will require dialysis Indications for dialysis include the following:

Volume overload with evidence of hypertension and/or pulmonary edema refractory to diuretic therapy

Persistent hyperkalemia Severe metabolic acidosis unresponsive to medical

management Neurologic symptoms (altered mental status, seizures) Blood urea nitrogen greater than 100–150 mg/dL (or

lower if rapidly rising) Calcium/phosphorus imbalance, with hypocalcemic

tetany Inability to provide adequate nutritional intake because

of the need for severe fluid restrictionKliegman: Nelson Textbook of Pediatrics, 18th ed.

Dialysis

Peritoneal dialysis may contribute to the dissolution of vascular thrombi by removing fibrinolysis inhibitors and circulating plasminogen activating inhibitor-1, thereby activating normal endogenous fibrinolytic pathways.


Hypertension

caused by overexpansion of intravascular volume and/or ischemia-induced activation of the renin-angiotensin system calcium channel blockers (such as

nifedipine or nicardipine) as the initial choice of antihypertensive

changed to ACE inhibitors in patients who appear to have long-term renal sequelae



Prevention

Antibiotics

Prevention of HUS by antibiotic therapy to treat E.coli intestinal infection or early HUS is a very controversial subject. antibiotic therapy at the stage of gastrointestinal infection

with Stx-E. coli increases—by approximately 17-fold—the risk for full-blown HUS. I antibiotic-induced injury to the bacterial membrane might favor

the acute release of large amounts of toxins. Other reports failed to show a higher risk for HUS associated

with antibiotic administration.

On the basis of available data, we suggest that in patients with Stx-E. coli gastrointestinal infection, antibiotics should be avoided unless in cases with sepsis.

Scheiring J, Andreoli SP and Zimmerhackl LB. Treatment and outcome of Shiga-toxin-associated hemolytic uremic syndrome (HUS). Pediatr Nephrol (2008) 23:1749–1760

Anti-motility agents

In children with hemorrhagic colitis due EHEC infection, the use of antimotility agents has been associated with a greater risk for developing HUS. Thus, antidiarrheal agents are usually avoided contributes to retention of Stx within the

colon, which could enhance absorption of the toxin

Scheiring J, Andreoli SP and Zimmerhackl LB. Treatment and outcome of Shiga-toxin-associated hemolytic uremic syndrome (HUS). Pediatr Nephrol (2008) 23:1749–1760

THANK YOU

Peritoneal Dialysis (PD) vs Intermittent Hemodialysis (IHD) vs Continual Renal Replacement Therapy (CRRT)PD IHC CRRT

BENEFITS Fluid removal + ++ ++ Urea and creatinine clearance + ++ + Potassium clearance ++ ++ + Toxin clearance + ++ + COMPLICATIONS Abdominal pain + - - Bleeding - + + Dysequilibrium - + - Electrolyte imbalance + + + Need for heparinization - + + Hyperglycemia + - - Hypotension + ++ + Hypothermia - - + Central line infection - + + Inguinal/abdominal hernia + - - Peritonitis + - - Protein loss + - - Respiratory compromise + - - Vessel thrombosis - + +


er conference co* concepcion * conti * corpuz * cosico * cruz * cruz

Documents

gestational history

family history kidney

w signs of dehydrationrenal

group of diseasemechanism

private doctorreferred

p75 pale

older children

bowel movementmetronidazole