Medicine Blended Assessment - A 45 Year Old Lady with Anasarca

The Complete details of the History, Examination and Investigations for this case are shared in the original blog post below by Dr. Alekya:

https://alekyatummala.blogspot.com/2020/09/45-yr-female-with-anasarca.html

  • 45 year old lady 
  • H/O Type 2 Diabetes Mellitus since 5 years
  • H/O Hypertension since 1 year
  • She  was apparently asymptomatic 6 months ago : Until she developed pedal oedema which aggravated on walking and relieved on rest 
  • It was associated with a Grade 3 Shortness Of Breath (SOB).
  • 5 days ago, she presented with progressively worsening Pedal oedema (Pitting type)  Abdominal distension  Facial puffiness → Decreased urine output
  • SOB even at rest
  • Chest pain on right side, non radiating with intermittent palpitations.
  • No H/O Fever, Burning micturition, Hematuria or Frothy urine.

Answer to Question 1 :

Provisional Diagnosis :

  • Acute on Chronic Renal Failure (ACRF) 
  • Diabetic Nephropathy (Grade 5 CKD) with Anemia and Hypertension associated with Retinopathy 
Anatomical Diagnosis :
  • Severe Injury to the gomeruli and tubules of the nephrons in the kidneys leading to AKI and End Stage Renal Disease (Interstitial Fibrosis, Tubular Atrophy and Glomerular Sclerosis)
Etiological Diagnosis :

  • Untreated Diabetes since 5 years ➡️ Microangiopathic changes ➡️ Diabetic Nephropathy ➡️ CKD since 6 months (GFR < 15 ml/min - End Stage Renal Disease) ➡️ Disruption of the Renin Angiotensin Aldosterone System (RAAS) ➡️ Due to decrease in renal perfusion (JGA) ➡️ Increase in Renin secretion :
      • 1. ➡️ Increase in Sympathetic Activity (HR, RR)
      • 2. ➡️ Increase in Aldosterone secretion lead to Tubular Na, Cl, water retention and K excretion (Fluid Overload, leading to Right Heart Failure which presented as fluid accumulation in the 3rd spaces - Pedal Edema, Facial Puffiness, Ascites, Pleural Effusion)
      • 3. ➡️  Arteriolar Vasoconstriction (Increase in BP - H/o Hypertension since 1 year, leading to Left Ventricular Hypertrophy - as seen in the EcG, which eventually lead to Left Heart Failure and Pulmonary Edema - H/o Shortness of Breath)
      • 4. ➡️ In the Pituitary gland, affected ADH secretion, which again lead to Water retention and decreased Urine Output (Anuria)
      • Anaemia is commonly seen in CKD (<10mg/dl) due to deficiency of Erythropoietin which is produced by fibroblasts in the interstitium. Angiotensin II (which is affected in RAAS) is also a physiologically important regulator of erythropoiesis. Anaemia also causes LVH. Microcytic Hypochromic anaemia is seen due to Anaemia of Chronic Disease and IDA.
      • Since Albumin and Red Blood cells were visible on Microscopy, there is a possibility of Nephrotic Syndrome, which should be ruled out by performing a biopsy.










    Source https://commons.m.wikimedia.org/wiki/File:Renin-angiotensin-aldosterone_system.svg#mw-jump-to-license

    Answer to Question 2 :

    Reasons behind the following :

    Azotemia :

    Interstitial and glomerular inflammation

    Synechiae formation and Sclerosis - Bowman's space is obliterated

    Urine cannot be filtered across the Bowman's space

    Misdirected Filtration 

    Urine is filtered into the mesangium and interstitium 

    Further fibrosis leading to reduced/absent creatinine clearance and raised serum creatinine 

    Anemia :

    • Deficiency of Erythropoietin
    • Anemia of Chronic Disease
    • Iron Deficiency Anemia
    • Increased PTH leading to bone marrow fibrosis
    • Uremia causing bleeding
    • Vitamin B12 and Folate deficiency

    Hypoalbuminemia :

    Diabetes

    Increase in Intraglomerular pressure due to Hyperfiltration (Stage 1)

    Loss of autoregulation (Increase in Intraglomerular pressure cannot be dissipated)

    Intraglomerular Hypertension

    Hypoalbuminemia and Proteinuria


    Acidosis :

    • Metabolic Acidosis due to increased serum uric acid, serum creatinine levels, impaired ammonia excretion, reduced tubular bicarbonate reabsorption and insufficient renal bicarbonate production.

    Answer to Question 4 :

    The indication/crucial factor for Dialysis :

    • Anuria due to reduced/absent Urine Output and Decreased eGFR = 7ml/min (<15 ml/min) which is suggestive of END STAGE RENAL DISEASE.
    • According to the MDRD equation for calculation of eGFR = 186 x (Creatinine/88.4)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if black).

    Answer to Question 5 :

    Factors other than diabetes and hypertension that led to her current condition could be :

    • Anemia
    • Vascular and Cardiac Disorders
    • Hyperkalemia
    • Uremia
    • Endocrine and Skin Manifestations


    Answer to Question 6 :
    • Diabetic Nephropathy is the most common cause of Nephrotic Syndrome in adults.
      • Diabetic Nephropathy is the most common cause of end stage renal disease (CKD)
    • The prognosis in this patient is very poor - Most patients who present with End Stage Renal Disease (CKD Type 5) die within 1 year because the Rate of Fall of GFR in Diabetic Nephropathy is 8 - 10 ml/min/year. 
    • Strongest risk factor for progression of CKD is Proteinuria and increased tubulo interstitial involvement
    • Tendency for CKD to progress independently of the underlying etiology occurs only after more than 50% nephrons are destroyed.
    • The Most Common Cause of Death in CKD patients is Coronary Artery Disease due to accelerated atherosclerosis.
    • Hence, CKD is an MI equivalent.
    My Inputs/questions related to the case:

    1. Menstrual History of the patient is essential to rule out other differentials like Preeclampsia.
    2. Any history of diarrhea? Any signs and symptoms of Hemolysis? To rule out Hemolytic Uremic Syndrome.
    3. Infections can cause Infection-Related Glomerulonephritis. 
    4. Mebranous Nephropathy and other conditions should be ruled out by performing a biopsy (Indication for biopsy - presence of RBCs on microscopy in the urine)
    5. How was CUE performed when there was Anuria?
    6. How long after the diagnosis of HTN does it take for Hypertensive retinopathy to develop?
    7. What are the other causes of Pulmonary edema?
    8. Why can't steroids be given in this case?
    9. ACE Inhibitors like Captopril, Enlapril can be used to treat Diabetic Nephropathy.

    Active Learning Discussion :

    1. Post Residency PG 1: Is this your provisional diagnosis?
    "Provisional Diagnosis :
    Diabetic Nephropathy (Grade 5 CKD) 
    Or the treating unit's?"
    MBBS UG Student 1: It's my diagnosis sir.

    2. Post Residency PG 1: "Severe Injury to the gomeruli and tubules of the nephrons in the kidneys leading to End Stage Renal Disease (Interstitial Fibrosis, Tubular Atrophy and Glomerular Sclerosis)"
    Where is the evidence of all that in your patient?
    MBBS UG Student 1: It can be found on biopsy, which wasn't performed on our patient. But generally in Grade 5 Diabetic Nephropathy - these structures are usually involved, from an anatomical standpoint.
    Post Residency PG 1: You need to clarify that in our patient that is your assumption. 

    3. Post Residency PG 1: "CKD since 6 months (GFR < 15 ml/min - End Stage Renal Disease"
    Evidence of the above in your patient?
     MBBS UG Student 1: I calculated the eGFR from the patients Serum Creatinine and other parameters using the GFR formula

    4. Post Residency PG 1: How do you know it's CKD and not acute renal failure?
    MBBS UG Student 1: She had pedal edema and SOB since 6 months which gradually progressed into full blown anasarca. I attributed this to the progressing stages of her Diabetic Nephropathy.
    CKD is > 90 days, whereas Acute Renal Failure occurs from 48 hours to 7 days.
    She is currently in grade 5 (End Stage Renal Disease) due to the presence of Uremia and GFR being <15ml/min.
    She also has proteinuria which is a strong risk factor for progression of CKD

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