Pathophysiology of Hemolytic Uremic Syndrome

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This paper is about the case study of a lady who has delivered a baby, and has been reported to have Hemolytic Uremic Syndrome, following delivery. She had no previous records of any such disorder, and her blood tests have not been very positive even after three days of treatment. A detailed discussion of the disorder, its prevalence, causes and symptoms has been included.

Hemolytic Uremic Syndrome

Hemolytic Uremic Syndrome (HUS) is a disease commonly found prevalent in young children and infants. It dates back to the year 1955, when Gasser and his coworkers found children suffering from a syndrome that led to acute hemolytic anemia and renal failure.

Hemolytic Uremic Syndrome is not only found in children, but is also reported to be found in adults (Mayo Clinic, 2009). The current case under study is that of a 25 year old female who is delivering a baby, but has been diagnosed with HUS after giving birth. The cause of the disease may be administration of oral contraceptives, or a bacterial infection caused postpartum. Infection present in the body arises due to toxic substances present in the intestine, which eliminate red blood cells. The production of red blood cells is impaired and the kidneys are affected due to the infection. The infection may be so sever so as to produce renal failure if not diagnosed and treated at the right time, and following treatment, the individual can be fully cured.

Causes of the Disease

The disease being a gastrointestinal disorder is caused by the bacteria Escherichia Coli, Shigella, and Salmonella. Being the most common cause of renal failure in children, it is on the rise, having spread to large numbers of children. HUS may also be caused by taking certain medicines such as mitomycin C or ticlopidine. Other elements present in the body may additionally cause HUS, due to infection (“Medline Plus”, 2009). Studies show that the most common bacteria is the E. coli O157:H7 (Cleary, TG, 1988) and causes life threatening diseases like the HUS (Louis & Obrig, 1995).

The cause of this disease has primarily been found to be the consumption of undercooked or raw meat. Studies have shown the disease to appear as a result of salad consumption during a youth camp too (Brooks, et.al, 2004). It may also be caused if a visit to a hospital to a diarrhea patient is made, or if there has been a recent trip to a zoo (Shapiro, W., 2007). One study has shown the disease to occur through contact with a contaminated building (Varma, et.al, 2003). This bacterial disease gives rise to plentiful toxins in the blood. The toxins cause the infection, and the most common causative factor is consuming contaminated meat. If meat is left undercooked, it mainly gets contaminated with bacteria such as E.Coli and Shigella. On the other hand, Salmonella and Yersinia as well as the Campylobacter species are causative agents to Hemolytic Uremic Syndrome (Shapiro, W., 2007). Serotypes of E.Coli also fabricate protein toxins similar to shiga toxins (Fraser, M., et.al, 2004).

Pathophysiology of the Disease

The HUS is caused by bacterial actions and the infections they leave behind in the body. It is preventable, if people are careful of what they eat, and how well the meat they consume is cooked (NKUHD, 2009). Diarrhea is firstly caused when a person is infected with the HUS. In 90% of the cases, diarrhea is reported and 10% are diagnosed with a respiratory infection too.

The leading toxins are formed due to the bacterium E.Coli. The other mediators include Shigella and various others which have been mentioned earlier. All these microbes produce shiga and shiga-like toxins, which are caused by the strains of the bacteria. The infectants undergo cytotoxic activity, and affect the vero cells. These are then called verotoxins. The VTEC or verocytotoxin producing Escherichia Coli cause diarrhea and HUS (Jenkins, et.al, 2003). Around 5-10% of people infected with Shiga-toxin Escherichia Coli are likely to be affected with HUS (Thorpe, C., 2004).

The E.Coli is transferred through contaminated food and unpasteurized milk consumption. It is difficult to prevent from such instances, as the intake of food infected with the bacteria is not a deliberate action, and neither does the food taste bad, or give an off odor. Therefore it is unavoidable in certain circumstances to refrain from such food that possesses the bacteria; the only thing that can be done is to cook all types of meat well till it is fully tender.

Another aspect of transfer of the bacteria causing HUS is the contamination of water. The public water supplies of communities may be infected with the bacteria causing HUS, leading to health problems upon consumption. If children are fond of petting animals, they may be at high risk of getting the bacteria transferred to their bodies, because cows possess the E.Coli in their gastrointestinal tracks.

There are certain viruses which also may cause HUS. HUS is associated with other diseases such as AIDS and cancer, and may also be caused due to some chemotherapeutic agents. One such agent is Mitomycin C, as aforementioned, which is administered in prostate or gastric cancer.

The disease is divided into two parts depending on whether the patient has had diarrhea. The patient under consideration in this case study does not show any diarrhea instance, and her baby was delivered without any complications. In adults, HUS usually takes the form of TTP, or thrombotic thrombocytopenic purpura. Basically they are the same thing, because the endothelial cells are injured. This destruction causes lesions in blood capillaries. All of the damage caused is due to the bacterial or viral toxins that are released in the body.

The difference between TTP and HUS is that TTP affects all areas like the heart, brain, intestines, skeletal muscles, etc., but the latter affects only the kidneys. The microthrombi are restrained specifically to the kidneys. In the kidneys, hyaline thrombi are viewed in the structure, of the Bowman’s capsule and glomerules. These thrombi are localized only to the kidney, and cannot be seen elsewhere. Detailed views of infected kidneys show them to be swelled up with some hemorrhages present on the outer layer.

HUS has also been seen to be associated with Streptococcus pneumonia (Erickson, et.al, 1994).

Symptoms of HUS

The symptoms of Hemolytic Uremic Syndrome include overall general weakness within a short period of time. There may be constant vomiting and diarrhea, which may also contain blood. Urination in the person is greatly decreased, and may also stop.

The early symptoms show bloody stools, weakness, fever, lethargy, and vomiting, whereas later symptoms show decrease in the urine formed, then absence of urine, bruises on the skin, paleness due to jaundice, and at times, seizures. However, some studies have shown that not all HUS patients have diarrhea (Kaplan, et.al, 1998).

Examinations for Testing for the Disease

There will be various exams to carry out when there is doubt that the patient is suffering from Hemolytic Uremic Syndrome. These tests are basically diagnostic tests, which would confirm for the disease.

Anemia will be diagnosed for sure because of the reduction in red blood cells. The hemoglobin content will be declining with time, until treatment is given. On the contrary, the white blood cells would be increased in the total CBC result. This is the complete blood count that needs to be analyzed for valid diagnosis of any disease (“Medline Plus”, 2009).

A physical exam conducted would show a swollen liver or spleen. A change in the nervous system occurs. The laboratory tests of the blood and urine show signs of protein and creatinine in the urine, and decrease in blood.

Explain the clinical symptoms of the patient

Clinical Symptoms of the Patient

The 25 year old lady, who has been admitted to a hospital for delivering her baby, is not shown to suffer from any illness or disease prior to the process of delivery. The delivery of the baby went on in a normal function with no complications. The problem aroused postpartum. After four hours of the baby’s birth, the mother was found to be suffering from oliguria.

Oliguria is a reduction of urine production. It may occur in persons of all ages, who are affected with renal disturbances. A reduction in urine production at times may be normal, but if it is less than 400 ml/d in adults, then it may be termed oliguria, and attention needs to be given to the problem. The patient is seen to produce lesser urine than she should, postpartum. The cause may also be the reduced intake of liquids, which has resulted in dehydration in the body. Since oliguria is an acute disorder, it may be reversed with treatment, and is not the cause of renal failure (Devarajan, P. & Williams, L., 2009).

The oliguria prevalent in the patient has caused reabsorption of salt, water and proteins in the kidneys due to the reduced amount of filtration taking place. This reduction of filtration is a temporary malfunctioning of the kidneys. She is also suffering from proteinuria, which is the accumulation of proteins in the kidneys and urine, as the name implies.

Proteinuria is caused by kidney malfunction. Proteins are essential for the body and help build up muscles of all the body parts, keep blood from clotting, and help build the immune system. When the nutrients enter a person’s body, during the digestive and absorption processes, the kidneys filter the essential elements the body requires, and eliminates the waste products through the urine. The proteins are normally too large to be filtered through the kidneys to be passed into the urine, unless there is a kidney malfunction or damage, as in the case of this patient. Her kidneys are probably damaged, causing the proteins to pass into the urine that is produced. The renal damage may be due to thrombogenesis (Chandler, W., et.al, 2002).

When the kidneys are not functioning properly, the filtration process is not taking place normally, and proteins are passed out of the body. When there is not enough protein in the body, all body functions and parts are affected. The blood does not take up the normal amount of fluid it is supposed to, causing water to accumulate in the hands and feet or other body parts. This fluid retention is known as oedema. The patient is suffering from oedema of the upper and lower extremities, due to the retention of the fluids caused by the inefficiency of the kidneys (NKUDIC, 2009).

Thus one disorder of the patient’s body is leading to the next, and the basic problem is that of renal disorder. Familial HUS may be inherited in adults, according to a study (Berns, et.al, 1992).

Explain the laboratory findings in relation to the diagnosis

Laboratory Findings in Relation to the Diagnosis

The laboratory findings show decreased hemoglobin and increased platelets. The serum creatinine of the blood is also increased. The readings have shown to exceed the normal range. In the urine analysis, the volume of the urine is very low compared to the normal rate. Results show the urine to be 305 ml/d; whereas the normal range is 1500-2000 ml/d. this is an indication of the ‘oliguria’ that was diagnosed.

The protein content of the urine is also increased, which indicates the proteinuria diagnosed. The two disorders of oliguria and proteinuria have caused the oedema in the body of the patient.

Using the following formula calculate the creatinine clearance (normal range 88-128 ml min-1) for this patient and comment on your findings.

Calculations

V = Volume of urine in ml / min = 0.219 ml/min
U_c= Concentration of creatinine in the urine = 476 mg/dl
B_c = Blood concentration of creatinine = 2.5 mg/dl
C_c = U_c x V/B_c
V = Volume of urine in ml min^-1
U_c= Concentration of creatinine in the urine
B_c = Blood concentration of creatinine

Normal

V = 1500-2000 ml / day
1500/1440 = 1.041 ml/min
2000/ 1440 = 1.39 ml / min
1 day = 24 hrs x 60 min = 1440 minutes

Patient

V = 305 ml/day
V = 305 / 1440 = 0.219 ml/ min (Volume of Urine ml per min)
Uc = 500-1500 mg/dl (Normal)
Uc = 476 mg / dl (Creatinine concentration in Urine of patient)
Bc = 0.6-1.2 mg/dl (Normal)
Bc = 2.5 mg / dl (Blood concentration of creatinine in patient)
N = 88-128 ml / min [ 500 x 1.04 / 0.6 ]
P = 476 (mg/dl) x 0.219 ml/min / 2.5 mg / dl
Creatinine Clearance of Patient = 104.244 / 2.5 = 41.7 ml / min

Calculate the anion gap (NR = 10-20 mmolL-1). Is this patient suffering from metabolic acidosis?

Anion Gap

In every balanced solution, equivalents of anions always equal to equivalents of cations.

[Na] + [other cations] = [Cl] + [HCO3] + [other anions]

Normal cations in the urine are Na⁺, K⁺, NH₄⁺, Ca⁺⁺ and Mg⁺⁺.

Normal anions are Cl-, HCO₃^–, sulphate, phosphate

Usually Na+ , K+, Cl- and HCO3- are measured. Rest is unmeasured anions (UA) and unmeasured cations (UC)

Na+ + K+ + UC = Cl- + HCO3- + UA

NR = 10-20 mmolL-1

Anions/Cations	Patients	Normal range	Analysis
Serum bicarbonate	23 mmol^-1	22-30 mmol^-1	N
Serum chloride	98 mmol^-1	95-106 mmol^-1	N
Serum sodium	134 mmol^-1	135-145 mmol^-1	N-marginally decreased
Serum potassium	5.0 mmol^-1	3.5-5.0 mmol^-1	N

Equation: Na+ + K+ + UC = Cl- + HCO3- + UA = 10-20 mmolL^-1(Normal range)

Patient’s: Na+ + K+ + UC = Cl- + HCO3- + UA

134mmol-1 + 5.0 mmol-1 = 98mmol-1 + 23 mmol-1

139mmol-1 = 121mmol-1

Urinary anion gap is 18mmol-1 which comes under normal range. Hence the patient is not suffering from metabolic acidosis.

Explain the laboratory findings. In your view is this patient getting any better?

Laboratory Findings and Patient’s Health Status

The laboratory findings, after three days, have shown no positive results. The hemoglobin is found to be reduced as compared to the formerly reduced reading. The serum creatinine is greatly increased. The blood urea nitrogen has also substantially, though it was in the normal range in the tests taken three days prior to these tests. Therefore, there is a new disorder of blood urea nitrogen in the blood.

What is the correct course of action for a patient presenting with haemolytic uraemic syndrome?

Course of Action for a HUS Patient

A patient suffering from Hemolytic Uremic Syndrome needs medical advice in order to cover up for the inefficiencies caused by the body. Since the kidneys are the main organs related to the HUS, a thorough kidney analysis needs to be made along with frequent urine tests, in order to define exactly what is wrong.

Since HUS has no particular medicine for its cure, the patient has to undergo dialysis or blood transfusions. No single medicine can cure this disease. The kidneys need to be treated for their normal functioning, which is yet another difficult process. Dialysis will be essential for a HUS patient who has diarrhea, (Constantinescu, et.al, 2004) so that the blood is filtered, since the kidneys have failed to perform normally. Blood transfusion is carried out to normalize the blood content present in the body. Some medicines may be administered to raise the blood pressure. Intravenous immunoglobin G is given at times. Lastly, a special diet is given to patients suffering from HUS (Kugler, M., 2009). Bilateral nephrectomy may also help cure HUS (Ruggenenti, et.al, 2001). Another solution for short term survival is plasma exchange therapy (Lara, et.al, 1999).

The lady in the case study will need to undergo the dialysis process, and have blood transfused, since her kidneys seem to have failed to function normally, and there is no single medicine that may be given for this disorder. Her health condition seems to be deteriorating with time, therefore, she should be put on a dialysis machine right away, so that the body starts functioning normally again. Being a new mother, she needs instant attention, so that she can pay attention to the newborn too.

References

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