Sunday, September 6, 2020

Bimonthly Clinical Case Assessment I

This is to discuss, understand and review clinical scenarios so as to improve my clinical competency via online e-logging clinical cases. The cases have been shared after the pt/their guardian signed an informed consent.

Case 1 https://alekyatummala.blogspot.com/2020/09/45-yr-female-with-anasarca.html?m=1  

Complete details regarding the case are in the mentioned link above. 

Brief history :

45  y/o female who is a known case of DM (on medication) since 5 yrs, HTN since 1 yr (on medication). 
  • Asymptomatic 6 months back, would develop PEDAL EDEMA ON AND OFF - WHICH AGGRAVATED ON WALKING AND RELIEVED ON REST + SOB GRADE 3 , WAS ASKED TO REDUCE FLUID INTAKE AND PRESCRIBED SOME MEDICATION.
  • 10 days ago - DEVELOPED PEDAL EDEMA (PITTING TYPE), PROGRESSED TO ABDOMINAL DISTENSION AND FACIAL PUFFINESS, WITH RT SIDED CHEST PAIN, NON RADIATING, WITH INTERMITTENT PALPITATIONS. REFERRED TO THE HOSPITAL DUE TO DERANGED RFT. 
  • IN HOSPITAL FINDINGS - 
1. PT WITH ABOVE COMPLAINTS + 3 DAYS ANURIA
2. PT C/C/C, WITH PALLOR +
3. ULCER ON RIGHT SOLE
4. AFEBRILE, BP = 180/80 mm of Hg 
5. P/A - distended 
(FOR ALL  INVESTIGATION DETAILS, PLS REFER TO THE LINK)

QUESTIONS TO BE ANSWERED 

1. What is your complete anatomic and etiologic diagnosis from the data available in the patient's online record linked above? (ignore the provisional diagnosis on admission mentioned in the case report)

Ans: THE PT HAS HAD H/O EDEMA AND SOB SINCE A FEW MONTHS INDICATING, THIRD SPACE ACCUMULATION  OF FLUID. THE EDEMA BECAME MORE GENERALISED RECENTLY, WITH ANURIA AND CHEST PAIN. 


EDEMA AND ANURIA CAN BE ATTRIBUTED TO KIDNEY DYSFUNCTION DUE TO DIABETIC AND/OR HYPERTENSIVE CHANGES IN THE RENAL TUBULE. AND, THIS LEAD TO ELECTROLYTE IMBALANCE LEADING TO METABOLIC ACIDOSIS DUE TO DECREASED BICARBONATE GENERATION AND REABSORPTION. 

CHEST PAIN COULD BE ATTRIBUTED TO A PROBABLE PLEURITIC CHEST PAIN (AGAIN DUE TO PROTEINURIA/ALBUMINRIA)

SOB COULD BE ATTRIBUTED TO ANEMIA, IN EARLIER INSTANCES BUT GRADE 4 SOB COULD BE DUE TO PLEURAL EFFUSION. 

FINAL DIAGNOSIS ACCORDING TO ME - 45 Y/O PT K/C/O DM & HTN WITH ACUTE KIDNEY FAILURE WITH ?PLEURAL EFFUSION, SEVERE METABOLIC ACIDEMIA, IRON DEFICIENCY ANEMIA,  LEFT VENTRICULAR HYPERTROPHY AND ?A HEALING ULCER ON RT SOLE. 


2) What are the reasons for her:

A. Azotemia 

Ans: She is a DM and HTN pt, both of which cause parenchymal modifications in kidneys. The resulting parenchymal changes lead to decreased ability of nephrons to filter certain substances. Creatinine and urea are important nitrogen containing compounds excreted in the urine normally. Due to the parenchymal modifications in kidneys and the resulting reduced ability of kidneys to filter, creatinine and urea accumulate in the serum leading to azotemia. 

B. Anemia -  

Ans: 1. India is a developing nation with prevalent gender based stereotypes and rigid patriarchial gender roles which leads to women always being deprived of basic nutrition and care. Which is why, anemia is prevalent in women in India. The following paper quotes 

Prevalence of anemia was high among all women, poor urban women had the highest rates and odds of being anemic“ 

https://pubmed.ncbi.nlm.nih.gov/12548297/

2. Kidneys produce ERYTHROPOIETIN, which is responsible for proliferation of blood cells in the bone marrow. Due to the gradual damage of kidney, it’s ability to produce erythropoietin also is reduced, which leads to anemia. 

C. Hypoalbuminemia 

Ans: Albumin is a low molecular weight protein synthesised by the liver, which is reabsorped in the kidneys and prevented from being excreted in the urine. Kidney dysfunction leads to increased excretion of albumin with (with no compensation in it’s synthesis by liver)  leading to decreased it’s serum concentration. 

Dysfunction of albumin reabsorption in the proximal tubules, due to reduced megalin expression, may explain the microalbuminuria in early-stage diabetes. Meanwhile, massive nonselective proteinuria is ascribed to various disorders of the glomerular filtration barrier, including podocyte detachment, glomerular basement membrane rupture, and slit diaphragm dysfunction in focal segmental glomerulosclerosis, membranous nephropathy, and other glomerulonephritis” 

https://www.hindawi.com/journals/ijn/2012/481520/

Decreased serum concentration of albumin leads to accumulation of fluid in third space, leading to Pitting oedema of various parts of the body, this is because, albumin(majorly) and a few other proteins contribute to capillary oncotic pressure on the venous end, which pushes fluid out of the vascular compartment into the interstitium.  

D. Acidosis 

Ans: Acidosis occurs due to either increased pCO2 or decreased HCO3-. There are mechanisms in our body to generate bicarbonate. 

1. Bicarbonate generation by erythrocytes 

2. Bicarbonate reabsorption and generation in kidneys 

In case of the pt, she is anemic, hence, CO2 diffuses into RBCs which are less in number, hence, decreased bicarbonate diffuses out ; there is no net gain of bicarbonate in the kidneys inspite of the urine being acidic.   

3) What was the rationale for her treatment plan detailed day wise in the record? Particularly mention rationale and  efficacy for some of the drugs administered such as oral and iv bicarbonate? When is iv or oral bicarbonate indicated and why is it contraindicated in certain situations? 

Ans

A. DAY 1 TREATMENT : 

1. Inj. NaHCO3 100 mEq , i.v. Stat in 100 ml NS 

2. Syrup POTCHLOR (KCl) 15 ml inn 1 glass water tid 

3. Withheld all OHA and Anti-Hypertensives 


NaHCO3- as treatment for  severe metabolic acidosis with AKI is a controversial subject as RCTs are yet to be conclusive; 

however, in BICARICU-1 trial, it was said that “in an overall non-selected group of patients with severe metabolic acidosis, SB infusion did not lead to a clinical outcome. But, SB infusion is efficient and safe to increase the arterial pH” 

and research conducted with severe-moderate AKI patients  “In the a-priori defined clinical stratum of patients with moderate to severe acute kidney injury (Acute Kidney Injury Network scores of 2 or 3 at enrolment), sodium bicarbonate infusion was associated with an improvement in the primary outcome (ie, composite criteria of organ failure at day 7 and any cause of death at day 28) and a reduced rate of mortality from enrolment to day 28 between the control group and bicarbonate group : 63% [95% CI 52-72] vs 46% [35-55]; p=0⋅0283. Additionally, the number of days alive and free from renal-replacement therapy was higher in the bicarbonate group than in the control group both in the overall study population and in the a-priori defined stratum of patients with moderate to severe acute kidney injury.”

https://clinicaltrials.gov/ct2/show/NCT04010630

a. Rationale according to me with respect to the given SB inj was to somehow neutralise the excess acid in the system with external SB

b. POTCHLOR SYRUP TO TREAT HYPOKALEMIA 

c. OHAs like Metformin, Anti-HTNs like ACE-Is, ARBs, Diuretics should be stopped and re-started when the pt is well 24-48 hrs later according to DAVIDSON 23rd Edition, Table 15.31, Page 481. 

B. DAY 2 TREATMENT:

a. Inj.HAI  according to sliding scale

a. t.OROFER xt bd

c. t.PAN 40 mg od

d. Inj.LASIX 40 mg iv bd if systolic bp >110mmhg

With patient’s acidosis showing signs of improvement and BP reducing from 180/80 mm of Hg to 130 mm of Hg, little changes could be done with respect to OHAs and Anti-HTN medication, but with extreme caution. 

This is because, according to https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956320/

 The use of diuretics was associated with adverse renal outcomes indicated by decline in eGFR and increasing risk of RRT initiation in our cohort of NDD-CKD patients. Therefore, it is cautiously suggested to carefully prescribe diuretics by keeping in view benefit versus harm for each patient.’’ 

Hence, only when BP is > 110 mm of Hg, diuretic has been administered. 

INJ HAI ACCORDING SLIDING SCALE is the best bet against OHAs like Metformin which are notorious for causing lactic acidosis. Even though the efficacy of sliding scale is less than the OHAs, it is preferred in this situation due to probable side-effects of other OHAs.

The efficacy of Sliding scale in a hospitalised diabetic pt according to https://pubmed.ncbi.nlm.nih.gov/7863803/

 The present study lends support to previous concerns that sliding-scale insulin therapy is less effective than preventive therapy in the management of hospitalised diabetic patients.” 

Tablet OROFER TX is to improve Iron deficiency anemia 

Tablet PAN is to prevent excess GI acid production

C. DAY 3 TREATMENT:

BP 170/90 mm of Hg with refractory ANURIA - central line was placed and dialysis was done. 

A. Inj.lasix 40mg iv bd - for regulating the increased BP and alleviating fluid retention 

B. tab.dytor 20mg of po

C. Inj.HAI S/C according to sliding scale

D. Tab.telma 40 mg od po->tab.nicardia 10 mg po/sos

Stopped telma - due to it’s side effects 

E. tab.orofer ct bd po

F. inj.erythropoietin s/c twice weekly - to promote hematopoiesis in bone marrow 

G.tab.nodosis 500 mg bd po - antacid

H.tab.shelcal ct po/op - calcium supplement 

I. syp.potcholr 15ml in one glass water tid

Renal replacement therapy - undertaken due to worsening of the condition of pt. 
 
D. DAY 4 TREATMENT

Pain abdomen with facial puffiness P/A - distended and tender , BP = 150/90 mm of Hg with normal ABG, but X ray shows fluid accumulation in thorax and abdomen 
 
Dialysis with blood transfusion done.  
Renal vein thrombus ruled out by Doppler. 
Above treatment continued. 

E. DAY 5 TREATMENT
Treatment above continued, following added 

1.Syp.lactulose 30ml bd - to treat constipation 
2.protein x powder 2tbsp in one glass milk bd
3.inj.MONOCEF 1gm IV bd - antibiotic cover


INDICATIONS FOR HCO3- 

FOR TREATING SEVERE METABOLIC ACIDOSIS,  
1. Kidney failure 
2. Diabetic ketoacidosis
3. Hyperkalemia (because acidosis leads K+ coming out of cells)


Contraindications -  
1. Alkalosis (after severe emesis)
2. Severe CKD 
3. Congestive Heart failure 

4) What was the indication for dialysing her and what was the crucial factor that led to the decision to dialyze her on the third day of admission? 

Ans:  REFRACTORY ANURIA (MAJORLY) , Other factors are - Metabolic Acidosis, HTN,  

5) What are the other factors other than diabetes and hypertension that led to her current condition? 

Ans: 1. Anemia - Anemia has accentuated the acidosis as 

DECREASED RBCs —-> DECREASED CO2 DIFFUSED IN RBCs —-> DECREASED HCO3- DIFFUSED OUT OF RBCs INTO THE SERUM —-> ACCENTUATING THE OVERALL EFFECT

2. Long-term use of ACE-I/ARBs, some NSAIDs

6) What are the expected outcomes in this patient? Compare the outcomes of similar patients globally and share your summary with reference links. 

Ans: According to https://clinicaltrials.gov/ct2/show/

“Persistent acidemia has been associated with poor prognosis, with a mortality rate as high as 57% when the pH stays below 7⋅20 more than 24h” 

                                     AND

 “ In intensive care settings, in-hospital mortality rates of moderate to severe AKI with severe acidemia has been reported to be over 50%”

IN THE ABSENCE OF HEMODIALYSIS, THE OUTCOME WOULD APPEAR MEEK. BUT SINCE THE PT IS SHOWING MINOR IMPROVEMENTS, I THINK THE OUTCOME WOULD BE JUST FINE. BUT AS THERE IS INCREASED CHANCE OF CONTRACTING INFECTION FIRSTLY, DUE TO FLUID RETENTION, AND SECONDLY DUE TO DIABETES, THERE IS ALWAYS A LOOMING RISK OF INFECTION, HENCE CONSTANT MONITORING OF VITALS WOULD BE NECESSARY.  


7) How and when would you evaluate her further for cardio renal HFpEF and what are the mechanisms of HFpEF in diabetic renal failure patients?

Ans: Most patients with Acute HF have a worsening of chronic HF with underlying worsening of anemia, renal disease, etc. The patient on admission has evidence of low perfusion (cold extremities) and congestion

ECG does show some evidence of LVH as V2S + V5R is not greater than 35, but is near it ; 

2D Echo - to look for systolic and diastolic function (not sure when to be done) 

Some index event, leads to compensation to maintain cardiac output by 

1. Activation of sympathetic system 

2. RAAS activation 

The above maintain cardiac output at the cost of cardiac remodelling. These compensatory mechanisms remain activated for a long period of time, and lead to HFpEF in pts with diabetes and renal disease. 

8) What are the efficacies over placebo for the available therapeutic options being provided to her for her anemia? 

Ans: According to http://www.finecurepharma.com/media/1103/managing-anemia-by-ferrous-ascorbateplus-folic-acid.pdf 

“ In a study regardless of the iron status, ferrous ascorbate showed the highest percent uptake, followed by ferrous bis-glycinate, whereas uptake from all other forms of iron was significantly lower. Recombinant erythropoietin is more expensive whereas ferrous ascorbate is better tolerated than ferrous sulphate plus additives”

9) What is the utility of tools like the CKD-AQ that assess the frequency, severity, and impact on daily activities of symptoms of anemia of CKD? Is Telegu among the 68 languages in which it is translated? 

Ans: According to https://jpro.springeropen.com/articles/10.1186/s41687-020-00215-8

 The CKD-AQ is a novel PRO measure that captures the frequency and severity of the most relevant symptoms and impacts associated with anemia of CKD” 

And 

Questionnaire (CKD-AQ), which includes 23 items assessing frequency and severity of the most relevant symptoms and impacts identified by patients with anemia of CKD. The CD interviews confirmed the clarity and relevance of the concepts identified in the CE phase.”

No, as far I know, Telugu is not. 

10) What is the contribution of protein energy malnutrition to her severe hypoalbuminemia? What is the utility of tools such as SGA subjective global assessment in the evaluation of malnutrition in CRF patients? 

Ans: PEM can lead to decreased RNA which lead to mechanisms leading to reduced synthesis of albumin, leading to hypoalbuminemia.

According to   https://www.medscape.com/answers/166724-41450/how-does-malnutrition-cause-hypoalbuminemia

 Deficient protein intake results in the rapid loss of cellular ribonucleic acid and disaggregation of the endoplasmic reticulum–bound polysomes and, therefore, decreased albumin synthesis”

Medical and healthcare data, should not be merely statistics. SGA and it’s evaluation of malnutrition helps in subjective analysis against standard ranges, making it less objective and patient oriented, and at the same time, population oriented. 



CASE 2 : https://bhavyayammanuru.blogspot.com/2020/09/aki-secondary-to-uti.html?m=1

11) Please comment on the differences in the diagnosis, therapy and outcomes in both these two patients. 

Ans: Case 2 pt appears to have some infectious etiology owing to the increased values in Total and Differential WBC count. In addition to azotemia and decreased urine output, there is decreased clotting factors, total proteins, albumin and ALP and increased bilirubin suggesting a hepatic etiology. 

Viral Infections like HBV, HCV are mostly ruled out. HIV test also is negative, but it also be false negative if patient is in window period. 

But, fever and cough suggest some index infectious event leading to the hepato-renal outcome. The USG shows no abnormality whatsoever, indicating that the renal parenchyma is normal. 

Diagnosis of case 2 - (?hepatic injury) Pre-renal AKI 

In Case 1, Pt has h/o congestive symptoms since a long time, with exacerbation of the same and anuria with metabolic acidosis. The condition here appears to be more severe as even cardiac function appears to be affected. 

Therapy wise, Case 2 his anti-hypertensive medications like Amlong (CCB) has been continues, with Inj HAI acc to sliding scale and antibiotics due to suspicion of an infection. But frequent monitoring of vitals, GRBS has been advised. 

In Case 1 all her anti-HTN and OHAs were stopped to first correct her acidosis, her electrolytes were imbalanced (more than Pt in case 2) , with gradual introduction of Anti-HTN medication with caution and Inj HAI acc to sliding scale.

Outcome of pts like in case 1 has been mentioned earlier. Pls refer to Answer 6. 

Outcome of to in case 2 according to  https://www.hindawi.com/journals/ijn/2015/108139/

 We present one of the only studies of US cohort examining implications of the etiology of AKI in cirrhosis. We showed a similar 90-day mortality rate between individuals with HRS and ATN, which was higher compared to the mortality in those with PRA”    

But it is to bear in mind, that the above research throws little light on infectious causes of pre renal azotemia. 

12) Would you agree with the provisional diagnosis shared for this  58 M in the online case report linked above?

Ans: Yes i do agree with the diagnosis, although more about the etiology could be known for localising the index site of insult and identifying the index event leading to the insult by looking farther into the history of patient and mindfully requesting investigations.

13) What are the findings in the ultrasound of both kidneys? How do you explain those findings? Would it explain the etiology for his renal failure? 

Ans: In case 1 - The kidneys though have normal size, are B/L raised echogenicity and partially lost cortico-medullary distinction (CMD) suggesting parenchymal insult, fitting with AKI due to renal cause as the diagnosis. 

In case 2, USG is normal. Suggesting some sudden event like infection , leading to AKI.

 


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