Study of Acid-Base Disturbances in Patients with Liver Cirrhosis

Background and study aim : Acid base disturbances occur frequently in the setting of liver diseases. As liver’s metabolic function worsen, particularly in the setting of renal dysfunction, haemodynamic compromise, and hepatic encephalopathy, acid base disorders ensue. The aim of this study was to assess acid base disturbances in patients with liver cirrhosis. Patients and Methods: The present study was conducted on 60 cirrhotic patients, as well as 20 healthy persons of matched age and sex as a control group. Diagnosis of cirrhosis was done by clinical examination, ultrasonographic findings and laboratory investigations. Patients and controls were subjected to the following:Full history taking, Thorough clinical examination, Abdominal ultrasound examination, Laboratory investigations including: CBC, Liver function tests, serum creatinine, Arterial blood gases to evaluate blood PH, HCO3, pressure of carbon dioxide and pressure of oxygen. Results: There was highly significant difference in PH, PCO2, PO2, and HCO3 and SO2 between both groups. The common acid base disorder was respiratory alkalosis. However, other disorders can be seen. Change in acid base balance was as following: Child's A group; no change in acid base balance. Child's B group; 75% no changes in acid base balance with 20% respiratory alkalosis and 5% metabolic alkalosis. Child's C group; 70% respiratory alkalosis with 15% respiratory acidosis and 15% metabolic alkalosis. Conclusion: These result declare the presence of multiple and mixed acid base disorder in cirrhotic patients


INTRODUCTION
The liver is an important organ in acidbase physiology.It is a metabolically active organ which may be either a significant net producer or consumer of hydrogen ions.The acid-base roles of the liver include: carbon dioxide production from complete oxidation of substrates, metabolism of organic acids anions such as lactate, ketone and amino acids.The conversion of ammonium (NH4) to urea in the liver, synthesis of plasma proteins: except immunoglobulins ]1[.Albumin is one of plasma proteins synthesized by the liver having many roles in acid-base physiology as it is considered as the major nonvolatile weak acid present in plasma, hypoalbuminemia causes a metabolic alkalosis.It is the major unmeasured anion in the plasma which contributes to the normal value of anion gap.It acts as an extra cellular buffer for CO 2 and fixed acids, thus an abnormal level can cause metabolic acid-base disorder ]2[.Hepatic disorders are often associated with acid base disorders.The most common disturbances in chronic liver diseases are respiratory alkalosis followed by metabolic alkalosis ]3[.Acid-base disturbances in patients with chronic severe hepatitis, liver cirrhosis, ascites and patients with hepatic encephalopathy is often alkalosis.Alkalosis indicates that the kidneys have increased their HCO 3reabsorption ]4[.This may result from toxic stimulation of respiratory center by ammonium from administration of alkalies as citrate in transfusions or with potassium supplements or from hypokalemia.Since urea synthesis consumes bicarbonate thus progressive loss of urea cycle capacity is associated with increased plasma bicarbonate level (metabolic alkalosis) and ammonia excretion by the kidney ]5[.Acid-base and potassium disorders occur frequently in the setting of liver disease.As the liver's metabolic function worsens, particularly in the setting of renal dysfunction, hemodynamic compromise, and hepatic encephalopathy, acidbase disorders ensue ]6[.Effective treatment of acid-base disturbance will be valuable in prevention of hepatic encephalopathy ]7[.The aim of present study was to evaluate the acid base disturbances in arterial blood gases in patients with liver cirrhosis.

PATIENTS AND METHODS
A total of 60 patients with liver cirrhosis were selected after giving a written informed consent, they were selected out from 200 patients admitted at Mansoura University Hospitals in the period between April 2013 and December 2013.They were 33 (55%) males and 27 (45%) females and their ages were ranging from 33 to 70 years, in addition 20

Demographics of the studied groups
There was no significant difference between the liver cirrhosis group and healthy controls and among subgroups of liver cirrhosis regarding the age and sex of patients.They were 33 (55%) males and 27 (45%) females and their ages were ranging from 33 to 70 years with a mean value of 41.35±5.81years in Group Ia, 53.95±7.51years in Group Ib and 55.35 ± 9.4 years in Group Ic.Manifestations of liver cell failure were present in various proportions of cirrhotic groups.HCV infection was present in the majority of cirrhotic patients, while HBV infection was absent.HCV-Ab and HBsAg were absent in all Group II persons.Ultrasonographic features of cirrhosis were present in all cirrhotic groups.Cirrhosis was mixed with peri-portal fibrosis in some patients of Group Ia, Ib and Ic.

Biochemistry of the studied groups
The mean value of hemoglobin concentration and platelet counts in cirrhotic groups (Ia,Ib,Ic) were significantly lower than that of Group II.
On the other hand, there was no significant difference between the studied groups as regard mean total leucocytic and RBCs counts (Table 1).The mean value of hemoglobin concentration in cirrhotic groups (Group Ia, Group Ib and Group Ic) were significantly lower than hemoglobin concentration in Group II (non cirrhotic).The mean value of platelet count of Group Ib and Group Ic were significantly lower than that of Group Ia.
The mean values of serum Bilirubin in Group Ib and Group Ic were significantly higher than that of Group Ia and Group II.The present study showed that the mean values of serum bilirubin in Group Ib and Group Ic were significantly higher than that of Group II and Group Ia.The mean value in Group Ic was significantly higher than that of Group Ia.While, there was no significant difference between Group Ia and Group II (Table 2).
The mean values of serum albumin in Group Ib and Group Ic were significantly lower than that of Group Ia and Group II.The mean values of INR were significantly higher in Group Ib than that of Group Ia and significantly higher in Group Ic than in Group Ia and Group Ib.
Meanwhile the values of INR in Group II were lower than that in Group Ib and Group Ic (Table 2).
The mean values of ALT in Group II and Group Ic were significantly lower than that in Group Ia and Group Ib.The mean values of AST in Group II were significantly lower than that in Group Ia, Group Ib and Group Ic (Table 3).

Acid base and electrolyte disturbances of the studied patients
In the present study initial assessment ABGs (Table 4) were done and both groups showed that significant difference in PH between Group Ic and Group Ia and Group Ib.As well as significant difference between Group II and Group Ic (Fig. 1).There was a highly significant difference in arterial PH, PCO 2 , PO 2 , HCO 3 and SO 2 between both groups.Also there was significant difference between Group Ic and Group Ia and Group Ib in PH, PCO 2 and HCO3.But there was no significant difference between both groups regarding serum Na + and serum K + levels.
The reported acid-base disorders in the studied groups revealed that Group Ia was normal, Group Ib: 20% respiratory alkalosis, 5% metabolic alkalosis and 75% normal, Group Ic: 70% respiratory alkalosis, 15% metabolic alkalosis and 15% respiratory alkalosis.There was highly significance difference between Group I and group II (Table 5).
The common acid base disorder was respiratory alkalosis (Table 5), however, metabolic alkalosis, respiratory acidosis and metabolic acidosis all could also be seen (Fig. 2).
Also PCO 2 there is significant difference (Table 4) between Group Ic and Group Ia and Group Ib.Again, there is significant difference between Group II and Group Ic (Fig. 3).
HCO 3 there is significant difference (Table 4) between Group Ic and Group Ia, Group Ib and significant difference between Group II and Group Ic (Fig. 4).
As regard SO 2 there is significant difference between Group Ib, Group Ic in relation to Group Ia as well as significant difference between Group II and Group Ib and Group Ic (Table 4).
There is low significant increase in serum Na + between Group Ib and Group Ic than Group II (Table 4).
As regard K + there is low significant decrease (Table 4) in Group Ic in relation to Group Ia and Group II in relation to Group Ic (Fig. 5).As regard INR it was significantly higher in Group Ib than in Group Ia and significantly higher in Group Ic than in Group Ia and Group Ib.Meanwhile the INR in GII lower than that in Group Ib and Group Ic, while prothrombin time was higher in cirrhotic patients than that of control patients.This could be explained by poor utilization of vitamin K owing to parynchymal liver disease ]22[.

The mean values of ALT and AST in Group Ic
were significantly lower than that in Group Ia and Group Ib.This may reflect the massive destruction and loss of viable hepatocytes ]23].
In present study initial assessment ABGs were done and both groups showed that significant difference in PH between Group Ic and Group Ia and Group Ib.As well as significant difference between Group II and Group Ic.This could be attributed to hypoxaemia, anaemia, hepatopulmonary syndrome, hepatic hydrothorax, hyperventilation which may be due to brain hypoxia and direct stimulation of respiratory centre by elevated progesterone level.Estradiol increase the number of progesterone receptors in animal and hence increase its overall actions ]16[.Also metabolic alkalosis may be due to the use of loop diuretics which lead to increase urinary hydrogen loss.High level of aldosterone may increase urinary hydrogen loss ]24[.
There is low significant increase in serum Na + between Group Ib and Group Ic than Group II.This could be explained by high level of aldosterone in case of hepatic fibrosis.
As regard K + there is low significant decrease in Group Ic in relation to Group Ia and Group II in relation to Group Ic which may be explained by by use of loop diuretics and high level of aldosterone.
Respiratory alkalosis is thought to be the most common acid base derangement found in patients with liver disease as a result of hyperventilation and an increase in blood ammonia levels.Funding: Non.

Conflicts of interest:
The authors declare no conflicts of interest.

Ethical approval:
The study was approved by the Ethical Committee of Menoufia Faculty of Medicine and a written informed consent was taken from each participant that follows principles in the Declaration of Helsinki.

Fig. ( 4 ):X 2 :
Fig. (4) : Results of Bicarbonate of studied groups (G: group) healthy persons of matched age and sex served as a control group.Diagnosis of cirrhosis based on clinical examination, ultrasonographic findings and laboratory investigations.

Table ( 1
): Haematological profile in studied groups G: group, RBCs: Red blood cells, WBCs: White blood cells, SD: standard deviation, P: Probability, a: significance relative to GIa, b: significance relative to GIb, c: significance relative to GIc

Table (
4) : Results of Arterial blood gases of studied groups suggested that metabolic alkalosis occurs as a result of abnormal hepatic bicarbonate disposal and urea synthesis in cirrhosis.However, Shangraw and Jahoor ]29[ showed that impaired urea synthesis may not precipitate metabolic alkalosis.Metabolic alkalosis often results from diuretic therapy with loop diuretics or thiazides and often is accompanied by hypokalemia.The administration of potassium or the use of potassium-sparing diuretics such as spironolactone may prevent or reduce metabolic alkalosis.Metabolic alkalosis also may occur in the setting of vomiting.As mentioned earlier, alkalosis, similar to hypokalemia, is thought to exacerbate hepatic coma; an increase in extracellular pH increases the conversion of ammonium to ammonia ]29[.CONCLUSIONRespiratory alkalosis either alone or associated with metabolic acidosis is most common acid base disorders.So we should put in our considerations the conditions which increase this state as gastric aspiration and vomiting.Other factors implicated in mediating changes in PH should be studied carefully such as septic shock or haemorrhage which may lead to a metabolic acidosis.We should put in our consideration that most minor therapies such as infusion of normal saline, administration of albumin, glucose infusion and initiation of diuretic therapy, vasopressin analogs and lactulose therapy may alter delicate acid-base balance.