Bimonthly Clinical Case Assessment II

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

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

ANSWERS FOR CASE 1 

Question 1. What is the reason for this patient's ascites? 

Ans - The patient is a chronic alcoholic and alcohol is well known to cause hepatocyte injury. 

In the initial stages, due to the immense regenerative property of the hepatic cells, the injury is reversed. 

• But in the later stages, as the alcohol consumption reaches chronicity, the injury predominates the regeneration of liver cells. 
• The injured liver cells and the Kupffer cells (macrophages of the liver) produce cytokines which activate Stellate cells (which also happen to store Vit A) 
• Activation of stellate cells (Which convert to myofibroblasts) starts a process ultimately leading to FIBROSIS OF LIVER TISSUE. 
• The fibrosis over time, with continuation of injury, modifies the hepatic architecture, leading to CIRRHOSIS. Where some part of the hepatic parenchyma is functional and some part is not. 
• This edificial modification leads to disturbance in hepatic vasculature. Leading to PORTAL HYPERTENSION. 

NOW, DAMAGE TO LIVER CAUSES TO MAJOR ISSUES (WRT THE QUESTION) 

1. DECREASED HEPATIC METABOLISM  

2. PORTAL HYPERTENSION

• THERE IS EVIDENCE  FROM THE Pt’s HISTORY 3 YRS AGO TO PROVE DECREASED HEPATIC METABOLSIM - RATHER, DECREASED PROTEIN SYNTHESIS 

1. B/L PEDAL EDEMA UPTO KNEE ( DECREASED ALBUMIN SYNTHESIS)
2. BLEEDING FROM GUMS  (DECREASED CLOTTING FACTOR SYNTHESIS) 

• PORTAL HTN, IS GENERALLY SEEN IN THE END, WHEN ONE COMES ACROSS A VARICEAL BLEEDING. WHICH IS, NOT SEEN IN THIS CASE. BUT THAT DOES NOT RULE OUT THE POSSIBILITY OF PORTAL HTN, AS PORTAL HTN CAN EXIST WITHOUT VARICEAL BLEEDING. ONLY WHEN THE PORTAL PRESSURE IS >12 mmHg, IS THE RISK FOR VARICEAL BLEED HIGHER. 

Cause of Ascites - 

1. Hypoalbuminemia - Due to decreased albumin, the oncotic pressure at the venous end of the capillaries falls, owing to which, the fluid does not shift from interstitium to vascular compartment. And the majority of the fluid, tends to remain in the interstitium. 

2. Portal hypertension - leads to splanchnic vasodilation (due to NO released in Portal HTN), And the systemic arterial pressure falls leading to activation of RAAS, which causes sodium and water retention. 

This leads to altered intestinal capillary permeability and accumulation of fluid in peritoneum. 

“Systemic arterial pressure falls due to pronounced splanchnic vasodilatation as cirrhosis advances. This leads to activation of the renin–angiotensin system with secondary aldosteronism, increased sympathetic nervous activity, increased atrial natriuretic hormone secretion and altered activity of the kallikrein–kinin system (Fig. 22.16). These systems tend to normalise arterial pressure but produce salt and water retention.’’ - Page 863, Davidson Textbook of medicine - 23rd Edition 

                                                              

Question 2. Why did the patient develop bipedal lymphedema? What was the reason for the recurrent blebs and ulcerations and cellulitis in his lower limbs?  

Ans - The B/L pedal edema is due to the same reason as above, hypoalbuminemia leading to decreased oncotic pressure, leading to fluid accumulation in the interstitium of dependent parts. 

And, INFERIOR VENACAVAL OBSTRUCTION ? 

1. The pt does have a history of lang standing pedal edema. It is possible that, because of the chonicity of pedal edema, the lowers layers of skin on the legs and feet underwent fibrosis and thickened with impaired neuro-vascular supply. Adding, the effect of probable nutritional deficiency (vit a, B12, Folate, Iron) lead to weakened skin, peripheral neuropathy. 

2. Due to the long standing pedal edema, the superficial veins dilated, the fluid exits through skin, in the form of blebs. Which, might get infected easily considering the impaired immunity (decresed immunoglobulin systhesis + pt consuming steroids ) and neuro-vascular supply to the lower limbs. These repeated infections might have lead to cellulitis.

The above is my hypothesis, cannot vouch for accuracy. Pls do intimate if it needs any correction.  

Question 3.  What was the reason for his asterixis and constructional apraxia and what was done by the treating team to address that?  

Ans. Liver metabolism of ammonia and urea is impaired. Leading to hepatic encephalopathy. 

1. Fluid restriction <1.5litres/day  
Salt restriction <2.4gms/day
2. Tab lasilactone (20/50)mg BD 
If SBP <90mmhg -avoid 
3.syp hepameiz 15 ml/PO/OD
4.IVF 1 NS slowly at 30ml/hr 
5.strict I/O charting 

Question 4. 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. 

Ans. Treatment given is aimed at increasing the fluid wash out with decresed fluid and salt administration and increased protein intake. Antibiotic cover to prevent new and worsening of present infected ulcer. H1-blocker and anti-emetic to prevent the probable side-effects to antibiotics.

1. Diuretics to increase fluid wash out and decrease edema - and to combat the diastolic dysfunction 

“Loop diuretics and aldosterone antagonists must be administered to the patients not responding to the previous regimen. Available evidence indicates that aldosterone antagonists are the first-choice drugs, as these substances are more effective than furosemide. Nevertheless, loop diuretics potentiate the effects of aldosterone antagonists. The reduced efficacy of furosemide in these patients, when compared with that of spironolactone, may be related to an impairment of both pharmacodynamics and pharmacokinetics’’ - 

https://pubmed.ncbi.nlm.nih.gov/7506337/

2. Vitamin K for decreasing further episodes of internal bleeding. But, cirrhosis can be hypercoagulable or hypocoagulable state. Vit K is given so as to correct PT in cirrhosis patients. 

“the practice of vitamin K supplementation in cirrhotic patients is not well defined, and its true value appears questionable.” 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385738/

3. Hepamerz for hepatic encephalopathy 

“L-ornithine-L-aspartate infusions were found to be effective in cirrhotic patients with hepatic encephalopathy.” 

https://pubmed.ncbi.nlm.nih.gov/18983791/

4. Udilive - as gall bladder is distended with thickened walls, there could be undetected gall stones in patients with such long lasting liver disease. It has a protective function. 

“(1) protection of injured cholangiocytes against toxic effects of bile acids, (2) stimulation of impaired biliary secretion, (3) stimulation of detoxification of hydrophobic bile acids, and (4) inhibition of apoptosis of hepatocytes”

https://pubmed.ncbi.nlm.nih.gov/15062194/

5. Nutritional supplemenatation with thiamine, with strict vitals monitoring and I/O Charting help to proactively prevent Cardiac/Renal Complications or act faster for a better patient outcome. 

6. FFP and PRBC transfusion as pt is severely anemic.

 With hemodilution and hypervolemia, there is increased stress on heart and lungs. 

ACUTE GI CONDITION CAUSING ALTERED SENSORIUM

CASE SCENARIO 7

CASE REFERENCES - 

- https://sowmyamutyala.blogspot.com/2020/05/hello-everyone.html?m=1

- https://a-blog-by-adityarayilla.blogspot.com/2020/05/medicine-posting-log.html?m=1

65 F, homemaker,  came with the chief complaints of  ALTERED SENSORIUM and

1. Fever - which is insidious in onset, low grade w/o chills and rigor, intermittent type since 2 days  
2. Loose Stools - watery, mucoid, non-blood stained, 10 EPISODES/DAY, w/o pain abdomen since 2 days
3. Vomitings - 1 episode, with food as content, non bilious 
4. Reduced Urine Output - Since 2 days, not associated with burning micturition
5. Facial Edema - Since 1 day

She has a known case of HTN, on medication ; She has Rt sided Hemiparesis with slurred speech owing to a Lt sided parietal lobe infarct since Oct 2019 and is on anti-platelet therapy.

ANALYSIS - 

Acute GI condition, possibly, Food Poisoning, leading to diarrhea, causing DEHYDRATION, leading to hypovolemia, and acute kidney injury/acute exacerbation of chronic kidney condition due to hypovolemia.

Pt might have been in an altered sensorium owing to the electrolyte imbalance due to dehydration followed by kidney injury.

FINDINGS ON PHYSICAL EXAMINATION - 

• Pt was unconscious 
• BP - 50/20 mm of hg
• PR - 67 bpm
• RR - 20cpm
• GRBS - 147 mg/dl - prediabetic ?

- Stabilization of the patient's vitals becomes a priority in such cases.

ANALYSIS - 

 Pt is unconscious with hypotension, bradycardia, tachypnoea ; with a h/o dehydration and kidney dysfunction.

MECHANISM OF THE ABOVE -

DIARRHEA

|

LOSS OF FLUID AND ALKALI [BICARBONATE] FROM THE INTESTINES

|

HYPOVOLEMIA AND ACIDOSIS 

|

DECREASED RENAL BLOOD FLOW AND GRADUAL FAILURE OF COMPENSATORY MECHANISMS

|

PROTEINURIA DUE TO KIDNEY INJURY

|

HYPOVOLEMIC SHOCK PRESENTING WITH ALTERED MENTAL STATUS, HYPOTENSION, BRADYCARDIA AND TACHYPNOEA 

MANAGEMENT - 

• Immediate fluid replacement  

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.

 

CASE SCENARIO : PARA-PARESIS III

CASE 3

COMPLETE CASE REF -

 https://hitesh116.blogspot.com/2020/05/elog-13th-may-2020.html?m=1

18 y/o M with CC of  difficulty in walking since 1 month,  was insidious on onset and gradually progressing reaching a point where he finds difficulty in climbing stairs, in holding chappals, standing after sitting ; he complains of PAIN in calf muscles with positive CALF TENDERNESS; there is h/o FEVER and WASTING of muscles ; h/o slipping off of chappals w/o knowledge ; h/o alcohol consumption twice every week.

NEGATIVE HISTORY - NO H/O SIMILAR DIFFICULTY IN UPPER LIMBS OR CRANIAL NERVE INVOLVEMENT ; NO H/O AUTONOMIC NERVOUS SYSTEM ISSUES  

ANALYSIS : PATHOLOGY COULD BE - 

• VASCULAR
• MUSCULOSKELETAL
• IN CNS
• IN PNS

POSITIVE FINDINGS ON CLINICAL EVALUATION

• Moderate built and poor nourishment 
• Pallor - present
• Bulk of the muscles in B/L UL and LL is decreased - suggesting wasting
• Hypotonia in B/L LL with normal UL
• Decreased Power in B/L LL with normal UL 
• Plantar Reflex is MUTE 
• Deep Tendon Reflexes are absent B/L in both UL and LL
• Positive Calf Tenderness

ANALYSIS BASED ON HISTORY AND CLINICAL FINDINGS :

18 y/o anemic pt with muscle pain, weakness, wasting. With mute plantar reflex and absent deep tendon reflexes in both B/L UL and LL with h/o slipping off of footwear w/o knowledge and  h/o fever.

It is an LMN Lesion which could be inflammatory along with peripheral neuropathy.

Points to be kept in mind for arriving at a differential diagnosis - 

• Age of onset
• Acute onset, pain, weakness with h/o fever 
• Weakness is symmetrical and gradually progressing in LL 
• Mental functions are intact
• No h/o intermittent claudication pain / edema in LL with skin changes, ruling out vascular pathology
• No h/o Diurnal Variation/relief on exertion of the weakness ruling out major NMJ disorders
• Pain could be due to compression of nerves/ pathology in muscle 

DIFFERENTIAL DIAGNOSIS WITH SPECIFIC INVESTIGATIONS :

• Polyneuropathy 

Etilogy is varied. Investigations required are as follows -

- GRBS, THYROID PROFILE, LFT, RFT to rule out endocrine, liver/ renal causes
- PERIPHERAL SMEAR to look for evidence of subacute combined degeneration of Spinal Cord
- Vitamins B12, B1, B6 , E deficiency ; Pyridoxine excess
- Alcohol induced
- Ruling out infectious causes ; ESR
- INFLAMMATORY CAUSES LIKE 

1. Gullian Barre - LUMBAR PUNCTURE, ELECTROMYOGRAPHY [EMG] , NERVE CONDUCTION STUDY [NCD]
2. Chronic Inflammatory Demyelinating Poyneuropathy - EMG, NSD, Sural Nerve Biopsy, USG of Peripheral Nerves
3. VASCULITIS DUE TO SLE/Sjogren's/Rheumatoid Arthritis/ Polyarteritis Nodosa - ESR, Anti-Nuclear Antibodies, Rheumatoid Factor, anti-CCP Antibodies

- Amyloidosis - tissue biopsy
- Could be Paraneoplastic
- Hereditary causes - Charc0t-Marie-Tooth-Disease/Familial Amyloidosis - NCS, Nerve Biopsy, Genetic Testing

• Radiculopathy due to intervertebral disc herniation in Lumbar region 

- B/L SCIATICA CAN BE CAUSED TO DUE SPINAL STENOSIS

-Spinal stenosis can be caused due to varied etiology 

-INVESTIGATIONS : 1. MRI and X-ray   2. CT myelogram 

- Physical test for confirmation of sciatica is Straight leg raise to produce Lazarević's sign. 

• Myopathies

- Becker's muscular dystrophy
- Limb Girdle muscular dystrophy
- Myopathies due to enzyme deficiencies
-Infections causing myopathies
- Systemic conditions like Sarcoidosis, etc

Most Myopathies can be detected by-

 EMG, NCS, CREAITINE KINASE LEVELS IN SERUM, MUSCLE BIOPSY AND GENETIC TESTING

INVESTIGATIONS DONE ON THE PATIENT

• Serology - All negative
• Chest X -ray - Normal
• Creatinine Kinase Levels - Normal
• T3 - Decreased
• NCS - Shows B/L common peroneal and sural axonal neuropathy.
• Sural Nerve Biopsy was planned
• Later pt was found to have Scabies also.

ANALYSIS- 

-Normal creatinine levels rule out anyform of active myopathy.

[Though Hypohyroid Myopathy can occur in some cases, but CK levels would be elevated in such cases]
- Common Peroneal Neuropathy is seen in Pts who are thin built/ sit cross-legged quite often/ wear tight-fitting foot-wear/Charcot-Marie-Tooth Disease/Polyarteristis Nodosa

DIAGNOSIS GIVEN TO THE PATIENT

Paraparesis secondary with B/L Common Peroneal and Sural Neuropathy with Scabies.

TREATMENT

• Tab PARACETAMOL 650 mg TID 

• Injection NEOMOL 100ml i.v. infusion if Temp increases >101 F

• PERMETHRIN 5% LOTION overnight, to be applied on entire body except face

• Tab B COMPLEX OD

CASE SCENARIO : PARA-PARESIS II

CASE 2

COMPLETE CASE REF -  https://hitesh116.blogspot.com/2020/05/12may-2020-elog-medicine-intern.html?m=1

18 y/o M presented with CC of -
B/L LL WEAKNESS SINCE 20 DAYS ; Started 2 y/o insidious on onset and gradually progressing, starting from proximal to distal region of both LLs.
H/o B/L Non pitting edema in LLs. 
He complains of difficulty in squatting and resuming upright position post-squatting, Difficulty in wearing and holding chappals.

NEGATIVE HISTORY - NO PROBLEM IN USING UPPER LIMBS AND NO HISTORY INDICATING CRANIAL NERVE INVOLVEMENT.

Priority Problems - 

• B/L LL Weakness leading to inability to perform daily chores.
• B/L LL Non pitting edema.

ANALYSIS - Pathology in

• VASCULAR - ARTERIAL/VENOUS
• CNS
• PNS
• MUSCULOSKELETAL SYSTEM

POSITIVE FINDINGS ON CLINICAL EXAMINATION 

 [For Complete examination pls refer the original case, link provided in the beginning]

• Power in both LL in 4/5
• Areflexia 
• Normal Sensory system with no meningeal/cerebellar signs
• GRBS - 142mg/dl

ANALYSIS AND DIFFERENTIAL DIAGNOSIS BASED ON KNOWN HISTORY AND CLINICAL FINDINGS

• ARTERIAL Cause is ruled out - no complaint of claudication pain.

• VENOUS cause - B/L Non pitting edema, Chronic Venous Insufficiency ?

• LYMPHATIC OBSTRUCTION - May lead to non pitting edema. Filariasis /Severe Infection/ Chronic Inflammatory Condition?

• CNS - Areflexia with muscle weakness rules out possibility of UMN Lesion. It is an LMN Lesion.

• PNS - Lumbo-Sacral plexus provides the nervous supply to LL and its compression presents with pain and other symptoms; BUT THERE IS EVIDENCE OF PERIPHERAL NEUROPATHY

• NEURO-MUSCULAR JUNCTION - Weakness could be Because of pathology in NMJ. Myasthenia Gravis and Lambert Eaton Myasthenic Syndrome fit the Pt profile to more extent than other NMJ disorders , this does NOT mean to say that the focus of damage is NMJ.

- Myasthenia Gravis : Sometimes patients with MG present with Limb muscle weakness only, even though most common symptoms are ocular and facial. There are atypical presentations as described in  -
https://pubmed.ncbi.nlm.nih.gov/27854225/?from_term=Myasthenia+gravis+limb+weakness&from_pos=5

''Patients with atypical/unusual MG onset were the 4.4% of all MG patients population. We describe seven different clinical categories: asymmetric distal upper limbs weakness, foot drop, isolated triceps brachii weakness and foot drop, post exertional axial weakness with dropped head, acute facial dyplegia, limb-girdle MG and MG with sudden lower limbs weakness and recurrent falls.''

But there is NO H/O FLUCTUATING WEAKNESS and ONLY LOWER LIMBS SEEM EFFECTED WHICH COUNTERS THE CLAIM w.r.t Myasthenia Gravis in this particular case.

- Lambert-Eaton-Myasthenic Syndrome : Effects proximal muscles of the limb and Lower limbs are more effected than upper limbs. BUT THE WEAKNESS IS RELIEVED AFTER ANY FORM OF EXERTION. 
From the history, one can infer that weakness was gradually progressive, hence LEMS is ruled out.

NMJ DISORDERS SEEM UNLIKELY, GIVEN THE PT HISTORY AND CLINICAL FINDINGS. 

• MUSCLE DISEASE : With defect in muscle itself, referred to as MYOPATHY .

Myopathies could be PRIMARY AND SECONDARY in nature. NOW, POINTS TO BE KEPT IN MIND WHILE ARRIVING AT THE DIFFERENTIAL DIAGNOSIS IS 

1. Slowly progressive, painless, symmetrical proximal lower limb weakness followed by distal limb weakness
2. Upper Limb Functions and other motor functions like speech, swallowing are intact
3. Mental functions intact
4. Age of onset - adolescence to early adulthood

Based on the above, DDs are - 

1. Becker's Muscular Dystrophy
2. Limb-Girdle Muscular Dystrophy
3. Sporadic late onset nemaline myopathy
4. Endocrine Myopathy
5. Polymyositis

DIFFERENTIAL DIAGNOSIS WITH SPECIFIC INVESTIGATION

• MYASTHENIA GRAVIS Class IIa

- Edrophonium Chloride Test
- Ice Pack Test
- Electrophysiological Tests :  REPETITIVE NERVE STIMULATION / SINGLE FIBRE ELECTROMYOGRAPHY

• BECKER'S MUSCULAR DYSTROPHY 

- Serum Creatinine Kinase [CK] Levels
- Electromyography [EMG]
- Muscle Biopsy
- Genetic testing

• POLYMYOSITIS 

- Serum Creatinine Kinase and Aldolase Levels
- Electromyography
- Electromyography

• LIMB GIRDLE MUSCULAR DYSTROPHY 

- ECG
- EMG
- Serum CK Levels
- MRI

• SPORADIC LATE ONSET NEMALINE MYOPATHY 

- EMG
- MRI
- Needle Biopsy

• ENDOCRINE MYOPATHIES 

- Serum TSH, T3, T4
- Serum Cortisol
- Serum PTH
- Serum Calcium

INVESTIGATIONS AND DIAGNOSIS DONE FOR THE PATIENT

Consists of abnormal findings, for complete investigations, pls refer to the link of the original reference.

• ELEVATED GRBS - 142mg/dl - PRE DIABETIC
• PERIPHERAL SMEAR - NORMOCYTIC NORMOCROMIC WITH LEUKOCYTOSIS
• ELEVATED TLC WITH LYMPHCYTOSIS 
• ELEVATED UREA, URIC ACID, CREATININE, PHOSPHORUS, CHLORIDE IN RFT
• ALBUMIN PRESENT IN URINE
• MUSCLE BIOPSY GIVES EVIDENCE OF ATROPHY/NECROSIS OF MUSCLE FIBRES ; IMPRESSION OF POLYMYOSITIS/MUSCULAR DYSTROPHY

DIAGNOSIS - MUSCULAR DYSTROPHY 

QUESTIONS -

• PT HAS ELEVATED LEVELS OF COMPONENTS IN RFT, OUT OF WHICH FEW ELEVATIONS CAN BE EXPLAINED w.r.t THE CORTICOSTEROID THERAPY AND SALICYLATE THERAPY, OTHERS ARE NOT. ALBUMIN IS SEEN IN URINE, COULD THE PT HAVE CHRONIC RENAL PATHOLOGY ?
• CHANGE IN MUSCLE WEAKNESS w.r.t TEMPERATURE ?
• HOW LONG HAS THE NON PITTING B/L LL EDEMA BEEN THERE ? DID IT CHANGE TO NON-PITTING TYPE OVER A PERIOD OF TIME?
• 2 YEARS IS A LONG TIME, DID THE PATIENT NOT SEE ANY OTHER PHYSICIAN ? RELEVANT DRUG HISTORY WHICH MIGHT HELP ?
• COULD HE BE PRONE TO DIABETES ?
• COULD THE REASON FOR B/L NON PITTING LL EDEMA BE MUSCULAR WEAKNESS WHICH LEADS TO DECREASED VENOUS RETURN AND VENOUS STASIS, OVER A PERIOD OF TIME CAUSING FIBROSIS ?

ANSWERS TO QUESTIONS POSED BY FACULTY 

• ANATOMICAL LOCATION OF LESION 

-  SKELETAL MUSCLE 

• MOST LIKELY ETIOLOGY AND PATHOLOGY 

- MUSCULAR DYSTROPHIES ARE 
     '' non-inflammatory degenerative conditions of muscle that are genetically determined, not effectively curable, and progressive. The types of muscular dystrophy are usually classified according to inheritance and distribution of weakness ''
https://www.dartmouth.edu/~dons/part_3/chapter_21.html#chpt_21_muscle

- Most common mutation is in the gene coding the PROTEIN DYSTROPHIN which is important for muscle contractions to occur. Age of presentation and severity depends on the severity of mutation in coding dystrophin and pattern of inheritance.

• THERAPEUTIC OPTIONS 

- NON PHARMACOLOGICAL 

1. AVOIDANCE OF INACTIVITY FOR A LONG DURATION

2. PHYSIO-THERAPY

3. ORTHOPEDIC APPLIANCES TO HELP IN MOTILITY, STABILITY AND SELF CARE.

-PHARMACOLOGICAL

- PREDNISONE HELPS IN PRODUCTION OF THE PROTIEN UTROPHIN WHICH RESEMBLES DYSTROPHIN AND SLOWS MUSCULAR DETERIORATION IMPROVING THE QUALITY OF LIFE.

The above is supported by a RCT linked below -

https://pubmed.ncbi.nlm.nih.gov/15642859/