Bi monthly assessment March.

 

1. https://ashakiran923.blogspot.com/2021/03/60-years-old-male-fever-under-evaluation.html?m=1

a). What is the problem representation of this patient and what is the anatomical localization for his current problem based on the clinical findings?How specific is his dilated superficial Abdominal vein in making diagnosis?

60 year old male chronic smoker & alcoholic non diabetic & non hypertensive

c/o fever since 15 days associated with burning micturition, on & off facial puffiness , abdominal distention , SOB Grade -2 which progressed to Grade -4 , aphthous ulcers & dysphagia.

O/E: Distended abdomen with dilated superficial abdominal veins

Shifting dullness +

Localization: Cirrhosis of liver with portal hypertension

UTI

AKI on CKD

Specificity of dilated abdominal veins :98%, sensitivity 42% in diagnosing hepatocellular disease.

b) What is the etiology of the current problem and how would you as a member of the treating team arrive at a diagnosis? What is the cause of his hypoalbuminemia?Why is the SAAG low?

The etiology of the disease in this patient could be a chronic history of alcoholism.

Based on his history & clinical findings : chronic alcoholism ----> cirrhosis of liver ----> portal HTN

1.cirrhosis of liver ----> reduced protein synthesis ----> decreased serum albumin ----> hypoalbuminemia. 

2.Hypoalbuminemia can also be due to either increased excretion of protein in urine - nephrotic syndrome (Low SAAG) 

3.or a long standing infectious etiology causing cachexia and hypoproteinemia (malnutrition / negative acute phase reactant)

Chronic smoking may be the cause of his apthous ulcers. 

LOW SAAG indicates non portal hypertensive ascites

1.It could be nephrotic syndrome causing Low saag ascites

2. https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/cld.537

However, the presence of low SAAG in the clinical context of suspected cirrhosis should be repeated because up to 3.3% of patients with portal hypertension may have SAAG less than 1.1 g/dL.7 A repeat paracentesis will often reveal a high SAAG.

A repeat sample of ascitic saag must have been done

c)Will PT,INR drangement preceed hypoalbuminemia in liver dysfunction??Share reference articles if any!

Coagulation and heamostasis is a dynamic process with interplay between primary heamostasis, coagulation, and fibrinolysis. Majority of plasma clotting factors and proteins of the fibrinolytic and anticoagulants are synthesized in the liver, while cell surface factors (surface factor is a transmembrane protein that acts as a receptor and cofactor for FVII) responsible for heamostasis are not synthesized by liver. Normal coagulation system has been conceptualized as Y shape pathway with separate intrinsic and extrinsic component initiated factor XII or factor VIIa/tissue factors leading to a common pathway of factor Xa/factor Va. In patients with severe liver disease, heamostasis is affected due to diminished synthesis of factors II, V, VI, IX, X, XI, XIII, fibrinogen, protein C, protein S, Vitamin K deficiency due to malabsorption or malnutrition, dysfibrinogenemia, enhanced fibrinolysis, diffuse intravascular coagulation, thrombocytopenia, impaired clearance of activated clotting factors, plasminogen activators, and fibrinogen degradation products. Clinical consequences of this may lead to abnormal bleeding test, bleeding, and thrombosis.

https://www.hindawi.com/journals/ijh/2011/695470/

There is no evidence that deranged coagulation preceeds hypoalbuminemia in cirrhosis.

d)What is the etiology of his fever and pancytopenia?

Etilogy of fever:UTI

Pancytopenia:

The liver plays a key role in both protein biosynthesis and lipid metabolism. As a result, hepatic synthetic dysfunction can have adverse effects on both cellular and soluble components of blood. Anemia may occur due to the hemolysis of acanthocytes (spur cells), which is ultimately due to abnormal lipid composition of the red blood cell membrane. Thrombocytopenia may result from several different mechanisms. Cytopenias also may be a consequence of hypersplenism. The liver is the primary site for synthesis of most procoagulant and anticoagulant proteins. The coagulopathy of liver disease is therefore complex. Early in the course of liver disease, thrombocytopenia and a coagulopathy associated with a prothrombotic state are not uncommon, whereas with more advanced disease pancytopenia and coagulopathy associated with hemorrhage become manifest. 

https://pubmed.ncbi.nlm.nih.gov/23953338/

e)Can there be conditions with severe hypoalbuminemia but no pedal edema? Can one have hereditary analbuminemia and yet have minimal edema? 

Please go this article https://www.frontiersin.org/articles/10.3389/fgene.2019.00336/full and answer the question

Inflammation and infection 

Albumin is considered a negative acute phase reactant, which means that as inflammation and other acute physiologic processes occur, its levels decrea

In liver disease:Albumin is synthesized in the liver, and low serum albumin can be indicative of liver failure or diseases such as cirrhosis and chronic hepatitis. If present, hypoalbuminemia is generally considered to be a sign of advanced hepatic cirrhosis, or irreversible damage to the liver

Malnutrition or malabsorption

Low albumin levels can also indicate chronic malnutrition from protein losing enteropathy.[3] This is often caused or exacerbated by ulcerative colitis, but can also be seen in cardiac disease and systemic lupus erythematosus

Conditions with severe hypoalbuminemia and no pedal edema- There can be a compensatory synthesis of protiens (globulins) other than albumin and thereby maintain the oncotic pressure in the intravascular compartment and preventing the extravasation of fluid. This could also be possible if there is a hypovolemic state in the same patient with hypoalbuminemia so that the pressures are again maintained and there is no fluid accumulation

It is possible for one with hereditary analbuminemia to not have pedal edema. Since it is a chronic and hereditary disease there can be compensatory synthesis of other plasma proteins

f) What is the efficacy of each of the drugs listed in his current treatment plan

Tamsulosin :

1.α1-Adrenergic receptor antagonists are used by 80% of physicians as the first agent to treat patients with benign prostatic hyperplasia (BPH) presenting with lower urinary tract symptoms (LUTS); 27 of 30 clinical trials have confirmed that α-blockers are effective for BPH treatment.

2.Tamsulosin's α1A subtype adrenergic receptor selectivity is considered to be responsible for its low cardiovascular side effects and lack of interaction with antihypertensives.

3.A 4-year extension, multicenter, open-label, phase IIIB clinical study evaluated long-term efficacy, safety, and tolerability of tamsulosin for up to 6 years; the study found a consistent statistically significant improvement in AUA symptom scores over 6 years, and most patients showed improvement during the first year that was sustained over 6 years.

4.the low incidence of acute urinary retention in patients treated with tamsulosin for up to 6 years suggests that tamsulosin may reduce the risk of AUR in patients with BPH.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1477608/

Nitrofurantoin

comparing 3 days of nitrofurantoin with placebo in young women with symptoms of UTI and pyuria found clinical cure rates of 70% versus 42%, respectively, 7 days after the start of therapy.

The prevalence of participants with side effects attributed to nitrofurantoin in the 17 studies generally ranged from 5% to 16%; nausea, abdominal discomfort and headaches were described. An exception was an open-label randomized controlled trial whose primary outcome was quality of life.

https://academic.oup.com/jac/article/70/9/2456/721364

CASE 2

45year old female with abdominal distension

https://navyamallempalli.blogspot.com/2021/02/dr_6.html

a). What is the problem representation of this patient and what is the anatomical localization for her current problem based on the clinical findings?

PROBLEM REPRESENTATION:

1.Abdominal distension since 2years

2.shortness of breath 

3.pedal edema since 2 months

4.cachexia_malnourishment

Anatomical localisation:

1.abdominal distension : causes: fluid,fetus,flatus,fat,feaces

Here in this case:

O/E: flankfullness and fluid thrill is present __indicates distension is because of fluid_ASCITIS

In this case the pattern is ascitis followed by pedal edema _clinically it indicates problem is in liver.

2.shortness of breath and dull note in right side _IAA,ISA,IMA and decreased breath sounds on right side indicates pleural effusion .most likely in this case pleural effusion is due to her refractory ascitis _HEPATIC HYDROTHORAX.

3.Cachexia _ is due to her loss of appetite which in turn because of massive ascitis .

Overall the major problem in this case_refractory ascitis since 2 years.

b) What is the etiology of her refractory ascites and pleural effusion? and how would you as a member of the treating team arrive at a diagnosis?

Sodium water retention due to underfill theory 

Increased portal pressure ( high SAAG) causing splanchnic vasodilation

And overfill theory is causing refractory ascites and hepatic hydrothorax is responsible for pleural effusion 

CAUSES OF REFRACTORY ASCITIS:

1.Non compliance to treatment

2.Tumor_hepatoma

3.Renal failure

4.spotaneous bacterial peritonitis

5.Portal vein thrombosis

6.NSAIDS

7.Infection

8.GI Bledding

 On ascitic fluid analysis: It is high SAAG and low protein ,it probably due to portal hypertension.

 she is on diuretics,frequent therapeutic paracentesis 

Her RFT was normal _no renal failure,

Noincreased cell counts in ascitic fluid, no features of infection _rule out SBP

No H/O 7se of NSAIDS 

On CECT abdomen_ no tumors identified in liver

No symptoms of GI bleeding:melena,hemetemesis.

So in this case most probably ascitis due to portal hypertension :

DD: cirrhosis of liver

Schistosomiasis

Portal vein outflow obstruction.

Cirrhosis is ruled out clinically no symptoms like jaundice,no coagulation disorders,no other signs of liver cell failure radiologically no altered echotexture,no shrunken liver,no nodules .

Stool microscopy was done to rule out schistosomiasis

Portal vein thrombosis evaluation done by triple phase cect followed byMR Venogram.

On triple phase CECT :Focal short segment of intrahepatic segment of IVC just below the diaphragm with normal hepaticveins And multiple osteosclerotic lesions in pelvis,ribs,vertebral bodies __sarcoidosis /metastasis.

MR Vengram_ suggested severe narrowing of intrahepatic portion of IVC___Chronic buud chiari syndrome.

PLEURAL EFFUSION:

When pleural and Ascitic tap done on same time sent for analysis _both looks like almost same _both are transudates:so, pleural effusion is most likely due to Hepatic hydrothorax.

DD: 1.sarcoidosis:

2.tuberculosis: pleural fluid and sputum for AFB and CBNAAT was negative.clinically no h/o TB.

3.Malignancy: pleural fliuid cytology was normal ,no dysplastic cells

c) Approach to a patient with ascites?Clinically is there any way to differentiate pre hepatic, post hepatic and hepatic causes?

Usually in pre hepatic causes of portal hypertension patient will have spleenomegaly and oesophageal varices but less chances of having ascites

In post and hepatic causes patients present with ascites

d)Causes of budd chiari syndrome?Why did the patient undergo bone biopsy?

IN THIS CASE BONE BIOPSY DONE FROM POSTERIOR ILIAC CREST ON LEFT SIDE TO EVALUATE THE OSTEOSCLEROTIC LESIONS IN PELVIS , RIBS, VERTEBRAE .

Patients with myeloproliferative disorders also developed budd chiari 

So to look for any myeloproliferative disorders and for any bone metastasis bone biopsy was done

d) Management strategies for refractory ascites and Budd chiari syndrome? Share the potential advantages and disadvantages of Peritoneal dialysis catheter placement in refractory ascites?

Management of refractory ascites

Management of BCS:

1.Diagnosis of BCS made by clinical features, laboratory and radiological investigations , management of underlying cause

2.Anti coagulant therapy with LMWH and then warfarin aim for INR 2_3

3.Treat the complications of portal hypertension with spirinolactone ,furosemide,and gastroscopy for variceal screening and band ligation

4.consider angioplasty /stenting for venous obstruction

5.consider TIPS if no improvement with anticoagulation , angioplasty, stenting.

6.TIPS fails /no improvement and acute liver failure consider liver transplantation.

7.Monitor chronic BCS for HCC by 6 monthly USG and alpha fetoprotein.

Peritoneal dialysis catheter in refractory ascitis:

Advantages:

Heamodynamic stability

Ascitis control directly and in continuing fashion

Easy catheter placement

Disadvantages:

Protein loss 

Over drainage of ascitis lead to hypotension

Dialysate leak or hydrothorax

Poor clearance owing to volume of ascitis

Higher infection risk .

e) What is the efficacy of each of the drugs listed in his current treatment plan 

Lasilactone:

https://www.medicines.org.uk/emc/product/907/smpc

Warfarin and LMWH

https://emedicine.medscape.com/article/184430-medication

f)What is the current outcome?and what could be the etiology of her current outcome?

Patient got expired on14th of march preceded h/o vomiting and nausea 

Cause of death was not confirmed, may be because of dislodgement of thrombus leading to pulmonary embolism.

CASE 3

55year old male with SOB and abdominal distension,orthopnea

https://jayanth1802.blogspot.com/2021/02/55-year-old-farmer-with-sob-abdominal.html?m=1

a). What is the problem representation of this patient and what is the anatomical localization for his current problem based on the clinical findings?

55 male chronic smoker & alcoholic k/c/o COPD with RHF (cor pulmonale) since 6 years

C/o abdominal distention & pedal edema since 1 year which aggregated from 1 week associated with SOB grade 3-4 , decreased urine output , on & off facial puffiness & anasarca

Based on the history & clinical findings his problem localization

COPD ----> RHF (corpulmonale) ----> Pre renal AKI (?CRS-1) & ?congestive hepatopathy

b) What is the etiology of his ascites? and how would you as a member of the treating team arrive at a diagnosis?Chart out the sequence of events.

COPD ----> RHF (corpulmonale) ----> Pre renal AKI (?CRS-1) & ?Congestive hepatopathy ----> Ascites

SAAG is 1.9 suggestive of portal hypertensive but low asctic protein of 2.1 and one of the important cause of high SAAG low protein is cirrhosis of liver which can be attributed to alcohol but USG abdomen shows normal liver.

So the other differential is heart failure causing ascites (but ascitic protein should be more than 2.5) 

But by going through the events it could be a mixed ascites.

c)What is the efficacy of each of the drugs listed in his treatment plan?

1. LASIX : Mortality: 3 placebo-controlled trials (n=221) reported data; the OR was 0.25 (95% confidence interval, CI: 0.07, 0.84, P=0.03), representing an absolute risk reduction of 8% in mortality in patients treated with diuretics compared to placebo.

Worsening of heart failure: 4 placebo-controlled trials (n=448) and 4 active-controlled trials (n=177) reported data. The OR was 0.31 (95% CI: 0.15, 0.62, P=0.001) for the placebo-controlled trials and 0.34 (95% CI:0.10, 1.21, P=0.10) for the active-controlled trials.

https://www.ncbi.nlm.nih.gov/books/NBK69174/

2. SALT AND FLUID RESTRICTION

https://pubmed.ncbi.nlm.nih.gov/23787719/

Individualized salt and fluid restriction can improve signs and symptoms of CHF with no negative effects on thirst, appetite, or QoL in patients with moderate to severe CHF and previous signs of fluid retention.

d)What are his current outcomes ?

Patient had cardiopulmonary arrest secondary to acute exacerbation of COPD with corpulmonale & severe PAH (Type-3)

QUESTION 4

Please go through the thesis presentation below and answer the questions below by also discussing them with the presenter

https://youtu.be/QlPrb1BSHGE

a) What was the research question in the above thesis presentation? 

To know the etiology of ascites based on SAAG 

b) What was the researcher's hypothesis? 

SAAG is better for etiological diagnosis of ascites than asctic fluid total protein as a marker

c) What is the current available sensitivity and specificity of SAAG in diagnosis of etiology of ascites

The sensitivity and specificity of SAAG were 100% and 87.8% respectively. Serum ascites albumin gradient is a reliable marker to differentiate ascites into portal hypertensive and non-portal hypertensive etiology. the presence of oesophageal varices is significantly associated with high SAAG levels.

When using the SAAG cut-off value 1.1 g/L, its sensitivity and specificity were 100.00% and 85.19% with an accuracy of 94.37%.

https://diagnosticpathology.biomedcentral.com/articles/10.1186/1746-1596-8-143#:~:text=When%20using%20the%20SAAG%20cut,%25%2C%20P%3C0.01).

5) Journal club questions on Ascites theme 

a) Please identify the study design and outcomes in the article linked here https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644216/ as well as the thesis linked here https://chandanavishwanatham19.blogspot.com/2021/03/of-thesis-clinical-profileevaluationdia.html

The study design was a prospective study and it showed that liver cirrhosis is the main cause of ascites among the 52 patients included in the study and next most common cause being heart failure and nephrotic syndrome

And the etiology of liver cirrhosis being HCV HBV virus.

Study design of thesis given

It is a prospective study

b) Please download the CASP diagnostic study checklist here https://casp-uk.net/casp-tools-checklists/ to evaluate the paper here https://www.hindawi.com/journals/ijh/2019/8546010/ and share your learning points on critical appraisal of the paper. 

c) Please evaluate this randomized controlled trial on different techniques at ascitic tap here: https://pubmed.ncbi.nlm.nih.gov/28233752/ also after downloading the randomized controlled trial CASP checklist here https://casp-uk.net/casp-tools-checklists/