October bimonthly assessment exam

Case 1

"57 year old man with jaundice, pedal edema and abdominal distension since three years and bleeding gums since three days"

https://swathibogari158.blogspot.com/2020/09/chronic-decompensated-liver-disease.html

Q1)What is the reason for this man's ascites?

A1) Although the casues for ascites are many, in this patient the ascites seems to be mainly because of the chronic damage to the liver which has lead to a condition called cirrhosis. It's progressed to decompensated type of cirrhosis due to the fact that the patient has developed complications like ascites, symptoms indicating hepatic encephalopathy etc.

When there is cirrhosis of the liver, there usually is an increase in the pressure in the portal vein which after a cascade of events (Increased venous pressure leads to release of vasodilating substances and vasodilation, with subsequent decrease in blood supply to the intestines, which is followed by activation of RAAS etc to maintain adequate blood supply to tissues)leads to accumulation of fluid in the peritoneal cavity(in the late stages of cirrhosis). There is activation of various modulating processes(RAAS, Sympathetic system etc) which eventually leads to sodium and water retention which after an extended presence leads to free water accumulation in the body cavities, along with dilutional hyponatremia because of the same(The recent Na+ levels show the same). 

Q2)Why did the patient develop bipedal lymphedema? What was the reason for the recurrent blebs and ulcerations and cellulitis in his lower limbs?  

A2) The patient seems to have developed bipedal edema due to a drastic fall in his albumin levels in blood. Albumin plays a very important role in maintaining intravascular volume by exerting a type of negative force called the Colloidal osmotic pressure. The colloidal osmotic pressure is responsible for the return of extravascular fluids at the capillary-venular junction. In this patient, There is a marked decrease in the albumin levels in blood due to the defective albumin synthesis probably due to the chronic derangement in liver function. As a result, due to gravity, subsequent increase in the hydrostatic pressure in the lower limb capillaries and decreased colloidal osmotic pressure in the venules of the lower limb, there is extravasation of fluid into the interstitial spaces leading to edema.

The recurrent blebs, cellulitis and ulceration were due to the marked edema of the lower limbs. The marked edema lead to a drastic fall in the efficient function of vascularity to the skin and nervous supply, which lead to derangement of the epithelium and formation of blebs, drying out of the skin and ulcers due to lack of awareness of dryness,injuries etc to the affected part, which progressed to cellulitis too as a result of poor hygiene, inefficient and ineffective dressing and poor medical therapy and diet.

Q3)What was the reason for his asterixis and constructional apraxia and what was done by the treating team to address that?

A3) Asterixis and constructional apraxia is most probably due to increased levels of ammonia in blood due to decreased clearance as in this patient due to a defective liver. These characteristic signs are used to grade HE with the help of an index called West Haven index.Ammonia at elevated levels is neurotoxic and is known to cause depression in mental state(pathognomonic of HE) and other features due to cerebral inflammation, astrocyte dysfunction etc which leads to asterixis and apraxia subsequently.

The treating team tried to tackle the HE with 2 drugs mainly i.e. lactulose and Hepamerz.

Lactulose acts on the intestinal bacteria and overall reduces the production of ammonia(lactulose is converted to lactic acid with acidification of the surrounding cell environment, this favors conversion of ammonium into ammonia and its subsequent entry into the intestinal lumen.

Hepamerz is composed of l-ornithine and l-aspartate.l-ornithine stimulates the urea cycle and both the compunds are substrates for glutamate transaminase which leads to elevated levels of glutamate, and ammonia is needed for the conversion of glutamate to glutamine, overall these drugs attempt to reduce the elevated ammonia levels in blood and thereby the symptoms and signs of HE.

Q3) What was the efficacy of each treatment intervention used for this patient? Identify the over and under diagnosis and over and under treatment issues in the management of this patient. 

A3) 

1. Fluid and salt restriction along with Diuretic such as Furosemide have been advised which is addressing the fluid overload status of the patient.
2. The patient has also been put on Antibiotics such as Augmentin and Metrogyl for his cellulitis. The swab culture report from the ulcer shows sensitivity to Augmentin.
3. Rifaximin and Lactulose is a frequently used combination in patients with Hepatic encephalopathy

Here's a randomized, double blinded controlled trial comparing Rifaximin plus lactulose versus the use of lactulose alone in patients with hepatic encephalopathy.

https://pubmed.ncbi.nlm.nih.gov/23877348/

P- 120 patients with overt Hepatic encephalopathy were randomized into two groups

I-Group A lactulose plus rifaximin 1,200 mg/day, 63 participants

Group B  received lactulose  plus placebo. This group had 57 participants.

C- Combination of rifaximin plus lactulose was found to be more effective than lactulose alone

O - 48 patients in group A compared to 29 patients in group B had complete reversal of hepatic encephalopathy. Reduced mortality in group A vs Group B - 23.8% vs. 49.1%. There were more deaths in group B because of sepsis compared to group A - 7 deaths in group A and 17 in group B. And patients on lactulose plus rifaximin had shorter hospital stay. There were no differences noted in GI bleed or hepatorenal syndrome. 

4) Syrup Hepamerz consists of L-ornithine, L- aspartate. This reduces the accumulation of ammonia.

This is a randomized prospective controlled trial carried out from May 2004 to February 2006 at Mexico city comparing L- ornithine L Aspartate to lactulose 

https://www.sciencedirect.com/science/article/pii/S1665268119319891

P- 20 participants with cirrhosis were included in this study.

I- 10 received LOLA  at a dosage of 9grams for 2 weeks ( 1 sachet containing 3 grams for 3 times a day) where as the other 10 participants received lactulose at a dosage of 30 ml per day for 2 weeks ( syrup containing 67 grams lactulose/100ml)

C- LOLA was found to be more effective in reducing hyperammonemic hepatic encephalopathy in Mexican patients with cirrhosis

O -  They were compared on the basis of mental state, number connection test, blood ammonia levels,asterixis, portal systemic encephalopathy index, EEGs, Quality of life assessment & GI side effects.

 Even though both the study groups showed improvement,, the participants receiving LOLA showed more improvement comparitively.

5) Udiliv contains ursodeoxycholic acid which has shown to reduce biochemical markers of cholestasis and hepatocellular damge in patients with chronic liver disease. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1379051/

Protein powder is needed since the patient has significant hypoalbuminaemia.

7) And also the Patient should've been started on a non selective beta blocker such a Carvedilol would have been effective in preventing recurrent epsiodes of GI bleed. 

Case 2 

A 54 year old male with cough,abdominal tightness,pedal edema and diarrhea.

https://sainiharika469.blogspot.com/2020/09/hello-everyone.html?m=1

Q1) Why were his antitubercular therapy stopped soon after his current admission? Was he symptomatic for ATT induced hepatitis? Was the method planned for restarting antitubercular therapy after a gap of few days appropriate? What evidence is this approach supported by?

A1) For this patient, the treating doctors seem to have withheld ATT after current admission mostly because of his deranged lft, which showed elevated liver enzymes and also as he was overall diagnosed with chronic liver disease after all clinical investigations and routine lab tests.

 

The ATT drugs rifampicin, isoniazid and pyrazinamide are known to be metabolized in liver by CYP3A4 enzyme and the metabolites are hepatotoxic, so with the patient already suffering from gross ascites assoc with chronic liver disease, it seems appropriate to stop att drugs for the present period of evaluation. 

It doesn't seem like he had symptoms of att induced hepatitis because Att drugs were started jus few days back and it takes a long time before the drugs can cause liver disease, although hepatotoxicity is identified by conjugated hyperbilirubinemia.

Guidelines for reintiating ATT were given by American thoracic society and British Thoracic society. 

https://www.thoracic.org/statements/resources/tb-opi/hepatotoxicity-of-antituberculosis-therapy.pdf

 'ACCORDING TO ATS - Treatment should be interrupted and, generally, a modified or alternative regimen used for those with ALT elevation more than three times the upper limit of normal (ULN) in the presence of hepatitis symptoms and/or jaundice, or five times the ULN in the absence of symptoms.

Q2)What were the investigational findings confirming the diagnosis of pulmonary TB in this man? 

A2) Sputum smear came positive for TB in the govt hospital, xray showed bilateral non homogenous opacities throughout the lung with fibrotic strands and cavities B/L. 

CT showed fibro-cavitatory changes and pleural thickening with interlobular septal thickening. 

Q3)What was the cause of his ascites?

Like the 1st case , this patient is suffering from liver cirrhosis and theres' portal hypertension and as answered for the above case due to a variety of mechanisms, theres accumulation of fluid in the peritoneal cavity, also in the lungs B/L homogenous opacities are seen on xray(lower lobes) along with mild right sided pleural effusion.

Q4)What are the efficacy of each intervention mentioned in his treatment plan and identify the over and under diagnosis as well as over and under treatment issues in it. 

A4) Protein powder is needed since the patient has significant hypoalbuminaemia.

5) I don't see the need for Piperacillin injections and nebulisation here. Instead the patient should've been started on second line ATT. And TIPS or liver transplant is further going to help the patient.

Case 3

47 year old man with bipedal edema since one year and abdominal distension since one month

https://sushma29.blogspot.com/2020/09/ascites-secondary-to-nephrotic-syndrome.html?m=1

Q1)What will be your further approach toward managing this patient of nephrotic syndrome? How will you establish the cause for his nephrotic syndrome? 

A1) fluid restriction <1l/day along with salt restriction <2g/day

2) And the patients are started on diuretics.

3) Anticoagulants if needed

Furthermore the patient on corticosteriods and Immunosuppresants though their efficacy has not been significantly proven yet.

The last to go option would be renal transplant could be through a live organ donar or through Jeevandhan program.

Renal biopsy helps in diagnosing the cause of the nephrotic syndrome

Q2) What are the pros and cons of getting a renal biopsy for him? Will it really meet his actual requirements that can put him on the road to recovery?

A2) The pros of the renal biopsy would be our ability to assess the prognosis of the disease, the cause of the disease and also how we're going to medically or surgically treat the patient.

The cons of the renal biopsy is the chance for him to develop secondary infections and also excessive unwanted bleeding that could occur after the biopsy.

All in all i dont think the renal biopsy would help the patient, because the patient would be either put on steroids or a combination of steroids and Immunosuppresants which would make him susceptible to further disease in the near future .

Here's a randomized controlled trial on cyclophosphamide and steroids in patients with idiopathic membranous nephropathy

https://jasn.asnjournals.org/content/18/6/1899

P- A total of 104 patients were recruited from March 1993 to February 1995: 53 patients in group 1 and 51 in group 2.

I - Patients were divided into two groups. 

Group 1 received supportive therapy that consisted of dietary sodium restriction, diuretics, and antihypertensive agents. 

Group 2 received a 6months course of alternate months of steroid and cyclophosphamide. 

The treatment regimen consisted of intravenous methylprednisolone 1 g/d for 3 consecutive days followed by oral prednisolone 0.5 mg/kg per d for 27 days in the 1st, 3rd, and 5th months and oral cyclophosphamide at 2 mg/kg per d in the 2nd, 4th, and 6th months. 

'Follow-up visits were scheduled every 2 weeks for 2 months, every month for 6 months, and thereafter every 6 months or more frequently when required. Parameters monitored included 24-h urinary protein and serum creatinine at each visit and serum albumin, cholesterol, and hemoglobin every 6 months.'

C - Treatment with a 6-mo regimen of cyclophosphamide and steroids induces remissions in a high proportion and arrests progression of renal insufficiency

O- 

'The course of proteinuria (A) and the Modification of Diet in Renal Disease (MDRD) estimated GFR (eGFR; B) during the follow up-period. ▪, group 1, ▴, group 2.'

Kaplan-Meier plots showing probabilities of dialysis-free survival (A), survival without reaching either end point (B), complete remission (C), and complete or partial remission (D). Solid line, group 1; dashed line, group 2.'

However, group 2 shows significant reduction in proteinuria and improvement in eGFR.

1.