Case report

1. Case report Zuzana Humlova Department of Pathophysiology

2. History • 1970 - hypertension related to fibromuscular dysplasia of the right renal artery; saphenous-vein bypass graft had failed, resulting in a poorly functioning right kidney • 1976 - developed angina pectoris • 1981 - diabetes mellitus was discovered, successfully managed with insulin therapy • 1995 - urea nitrogen level 12 mmol/l, creatinine 114.9 umol/l

3. 1997 - coronary artery bypass grafting, cardiac ultrasonographic examination performed slight widening of the left ventricular outflow tract, with Doppler evidence of mitral regurgitation • 1998 - bilateral carpal tunnel syndrome developed, and the patient began to have nocturnal „burning pain“ in her feet, with loss of vibratory sensation

4. 1 month later, proteinuria developed, increasing peripheral edema, diuretic medication caused frequent orthostatic hypotension and syncope • 1999 - intermittent constipation and diarrhea develop, with normal findings on stool examinations • - the splenic tip was palpated 4 cm below the left costal margin • - a ventricular-demand, dual chamber electronic pacemaker was implanted because of syncope associated with complete atrioventricular block • 2000 – intermittent claudication, voice became weaker, with hoarseness and a nonproductive cough

5. First admission • The patient was admitted to the hospital because of increasingly frequent episodes of syncope, her blood pressure in the upright position was as low as 60/40 mm Hg, and a new grade 2 systolic murmur was heard. There were peripheral edema.

6. Laboratory- I. admission • urea (mmol/l) 14.63 • creatinine (umol/l) 353.6 • protein (g/l) 52 • albumin (g/l) 12 • TSH (μU/ml) 14.3 • T4 (nmol/l) 68.21 • Iron 3.1 • Iron-binding capacity (μmol/l) 25 • Urine: specimen of urine 24 h: 9,57 g of protein, 0,462 g • of creatinine

7. Cardiac ultrasonographic examination • left ventricle - marked concentric hypertrophy; estimated ejection fraction, 65 %; mitral valve - calcification of the annulus, papillary-muscle displacement; aortic valve – cusp thickening; without stenosis; right ventricle – wall thickening; estimated systolic pressure 42 mm Hg; Doppler study – moderate mitral regurgitation, mild aortic, tricuspid, and pulmonary regurgitation.

8. Second admission: • 6 weeks after discharge, the patient was readmitted. Her edema began increase, with worsening dyspnea and more frequent anginal attacks. TT 37,1 C, BP 110/50, P 68, grade 3 systolic murmer over precordium and at the apex. The spleen was palpated 9 cm below the costal margin. Peripheral edema, vibratory sensation was impaired

9. Laboratory – II. admission • urea (mmol/l) 12.675 • creatinine (umol/l) 380 • protein (g/l) 51 • albumin (g/l) 13 • calcium (mmol/l) 1.95 • phosphorus (mmol/l) N • glucose (mmol/l) 5.66 • Sodium (mmol/l) 142 • Potassium (mmol/l) 2.8 • Chloride (mmol/l) 101

10. Hematologic findings • Hematocrit 26.3 • MCV 88 • White-cell count (per mm3) 9.000 • Platelet count (per mm3) 505.000

11. ECG • normal rhythm P 76/min, first-degree AV block (208 msec), and a pattern indicative of an old anterior myocardial infarction, with nonspecific ST-segment and T-wave abnormalities and very low voltage in extremity leads.

12. Radiograph of the chest showed slight cardiac enlargement and a moderate increase in bilateral pleural effusions. The leads of a dual-chamber electronic pacemaker appeared intact. Abdominal radiograph showed moderate splenomegaly and calcifications in the splenic and common iliac arteries.

13. SUMMARY OF EXAMINATIONS: • nephrotic syndrome • heart failure (restrictive cardiomyopathy according to clinical findings, ECG, Doppler +US) • bilateral sensory neuropathy • bilateral carpal tunnel syndrome • hoarseness • hypothyroidism • splenomegaly • normocytic anemia • thrombocytosis • diabetes mellitus • orthostatic hypotension • intermittent constipation and diarrhea

14. 1. TASK • What is the origin of peripheral edema? When can we find the nephrotic syndrome (NS)? • primary retention of Na and water, hypoproteinemia, heart failure • FSGN, MN, MZ, diabetic nephrosclerosis, SLE, amyloidosis

15. 2. TASK • What is typical for the NS? What are the complications of NS? • infection, thromboembolic disease, changes in lipids metabolism, protein malnutrition

16. 3. TASK • Restrictive cardiomyopathy was considered as a diagnosis. What can cause this disease? • Myocardial (noninfiltrative disorders-idiopathic disease, familial, hypertrophy, scleroderma, DM, pseduxanthoma elasticum, infiltrative disorders- amyloidosis, sarcoidosis, m. Gaucher, m. Hurler, fatty infiltration, storage disorders- hemochromatosis, m. Fabry, glycogen storage disease) • Endomyocardial (fibrosis, hypereosinophilic sy, carcinoid, metastatic cancer, exposure to radiation, toxins, anthracycline, serotonin, busulfan, mercurial agents)

17. 4. TASK • Why had she angina pectoris? What is the source of rhythm abnormalities? 5. TASK • What is the main cause of peripheral sensoric neuropathy?

18. 6. TASK • Why had she an orthostatic hypotension? Is there any convince with intestine dyscomfort? 7. TASK • How to explain splenomegaly and thrombocytosis together?

19. What type of systemic disease can be considered as a final diagnose?

20. AMYLOIDOSIS • systemic • topic • senile • 14 different proteins-SAA, monoclonal lambda or kappa Ig light chains, mutant transthyretin,cystatin, ANP

21. AL (primary amyloidosis) • monoclonal lambda or kappa Ig light chains produced by a clonal plasma-cell dyscrasis • ATTR (familial) • mutant transthyretin • AA (secondary) • amyloid A protein produce in response to a chronic inflammatoy state

22. Anatomical diagnosis: • Systemic amyloidosis, AL type (serum protein electrophoresis showed IgG lambda M components), with restrictive cardiomyopathy and involvement of the kidney, spleen, larynx, blood vessels, and peripheral nerves.

23. Heart failure Autonomic nervous system involvement Macroglossia hoarsenes Carpal tunnel sy Peripheral nervous system involvement Thrombocytosis AL AMYLOID Splenomegaly Anemia Hypofunction of adrenal glands hypothyreosis Hepatomegaly Nephrotic syndrome