Case reportCase report

Zuzana HumlovaZuzana HumlovaDepartment of PathophysiologyDepartment of Pathophysiology

HistoryHistory

19701970 - hypertension related to fibromuscular - hypertension related to fibromuscular dysplasia of the right renal artery; saphenous-dysplasia of the right renal artery; saphenous-vein bypass graft had failed, resulting in a poorly vein bypass graft had failed, resulting in a poorly functioning right kidneyfunctioning right kidney

19761976 - developed angina pectoris - developed angina pectoris 19811981 - diabetes mellitus was discovered, - diabetes mellitus was discovered,

successfully managed with insulin therapysuccessfully managed with insulin therapy 19951995 - urea nitrogen level 12 mmol/l, creatinine - urea nitrogen level 12 mmol/l, creatinine

114.9 umol/l114.9 umol/l

19971997 - coronary artery bypass grafting, - coronary artery bypass grafting, cardiac ultrasonographic examination cardiac ultrasonographic examination performed slight widening of the left performed slight widening of the left ventricular outflow tract, with Doppler ventricular outflow tract, with Doppler evidence of mitral regurgitationevidence of mitral regurgitation

19981998 - bilateral carpal tunnel syndrome - bilateral carpal tunnel syndrome developed, and the patient began to have developed, and the patient began to have nocturnal „burning pain“ in her feet, with nocturnal „burning pain“ in her feet, with loss of vibratory sensationloss of vibratory sensation

1 month later1 month later, proteinuria developed, increasing , proteinuria developed, increasing peripheral edema, diuretic medication caused peripheral edema, diuretic medication caused frequent orthostatic hypotension and syncopefrequent orthostatic hypotension and syncope

19991999 - intermittent constipation and diarrhea - intermittent constipation and diarrhea develop, with normal findings on stool develop, with normal findings on stool examinationsexaminations

- the splenic tip was palpated 4 cm below - the splenic tip was palpated 4 cm below the left costal marginthe left costal margin

- a ventricular-demand, dual chamber - a ventricular-demand, dual chamber electronic pacemaker was implanted because of electronic pacemaker was implanted because of syncope associated with complete syncope associated with complete atrioventricular blockatrioventricular block

20002000 – intermittent claudication, voice became – intermittent claudication, voice became weaker, with hoarseness and a nonproductive weaker, with hoarseness and a nonproductive coughcough

First admissionFirst admission

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

Laboratory- Laboratory- I. admission I. admission urea (mmol/l) 14.63 urea (mmol/l) 14.63 creatinine (umol/l) 353.6 creatinine (umol/l) 353.6 protein (g/l) 52protein (g/l) 52 albumin (g/l) 12 albumin (g/l) 12 TSH (μU/ml) 14.3 TSH (μU/ml) 14.3 T4 (nmol/l) 68.21 T4 (nmol/l) 68.21 Iron 3.1 Iron 3.1 Iron-binding capacity (μmol/l) 25 Iron-binding capacity (μmol/l) 25

UrineUrine: specimen of urine 24 h: 9,57 g of protein, 0,462 g: specimen of urine 24 h: 9,57 g of protein, 0,462 g of creatinine of creatinine

Cardiac ultrasonographic Cardiac ultrasonographic examinationexamination

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

Second admission:Second admission:

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

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

Hematologic findingsHematologic findings

Hematocrit 26.3Hematocrit 26.3 MCV 88MCV 88 White-cell count (per mm3) 9.000 White-cell count (per mm3) 9.000

Platelet count (per mm3) 505.000Platelet count (per mm3) 505.000

ECGECG

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

Radiograph of the chestRadiograph of the chest showed slight cardiac enlargement and a showed slight cardiac enlargement and a moderate increase in bilateral pleural moderate increase in bilateral pleural effusions. The leads of a dual-chamber effusions. The leads of a dual-chamber electronic pacemaker appeared intact.electronic pacemaker appeared intact.

Abdominal radiographAbdominal radiograph

showed moderate splenomegaly and calcifications in the splenic and common iliac arteries.

SUMMARY OF EXAMINATIONS:SUMMARY OF EXAMINATIONS: nephrotic syndromenephrotic syndrome heart failure (restrictive cardiomyopathy according to clinical heart failure (restrictive cardiomyopathy according to clinical

findings, ECG, Doppler +US)findings, ECG, Doppler +US) bilateral sensory neuropathy bilateral sensory neuropathy bilateral carpal tunnel syndromebilateral carpal tunnel syndrome hoarsenesshoarseness hypothyroidismhypothyroidism splenomegalysplenomegaly normocytic anemianormocytic anemia thrombocytosisthrombocytosis diabetediabetess mellitus mellitus orthostatic hypotensionorthostatic hypotension intermittent constipation and diarrheaintermittent constipation and diarrhea

1. TASK1. TASK

What is the origin of peripheral edema? What is the origin of peripheral edema? When can we find the nephrotic syndrome When can we find the nephrotic syndrome (NS)? (NS)?

primary retention of Na and water, primary retention of Na and water, hypoproteinemia, heart failure hypoproteinemia, heart failure

FSGN, MN, MZ, diabetic nephrosclerosis, FSGN, MN, MZ, diabetic nephrosclerosis, SLE, amyloidosis SLE, amyloidosis

2. TASK2. TASK

What is typical for the NS? What are the What is typical for the NS? What are the complications of NS?complications of NS?

infection, thromboembolic disease, infection, thromboembolic disease, changes in lipids metabolism, protein changes in lipids metabolism, protein malnutrition malnutrition

3. TASK3. TASK Restrictive cardiomyopathy was considered as a Restrictive cardiomyopathy was considered as a

diagnosis. What can cause this disease?diagnosis. What can cause this disease? MyocardialMyocardial (noninfiltrative disorders-idiopathic (noninfiltrative disorders-idiopathic

disease, familial, hypertrophy, scleroderma, DM, disease, familial, hypertrophy, scleroderma, DM, pseduxanthoma elasticum, infiltrative disorders- pseduxanthoma elasticum, infiltrative disorders- amyloidosis, sarcoidosis, m. Gaucher, m. Hurler, amyloidosis, sarcoidosis, m. Gaucher, m. Hurler, fatty infiltration, storage disorders- fatty infiltration, storage disorders- hemochromatosis, m. Fabry, glycogen storage hemochromatosis, m. Fabry, glycogen storage disease)disease)

EndomyocardialEndomyocardial (fibrosis, hypereosinophilic sy, (fibrosis, hypereosinophilic sy, carcinoid, metastatic cancer, exposure to carcinoid, metastatic cancer, exposure to radiation, toxins, anthracycline, serotonin, radiation, toxins, anthracycline, serotonin, busulfan, mercurial agents)busulfan, mercurial agents)

4. TASK4. TASK Why had she angina pectoris? What is Why had she angina pectoris? What is

the source of rhythm abnormalities?the source of rhythm abnormalities?

5. TASK5. TASK What is the main cause of peripheral What is the main cause of peripheral

sensoric neuropathy?sensoric neuropathy?

6. TASK6. TASK Why had she an orthostatic Why had she an orthostatic

hypotension? Is there any convince with hypotension? Is there any convince with intestine dyscomfort?intestine dyscomfort?

7. TASK7. TASK How to explain splenomegaly and How to explain splenomegaly and

thrombocytosis together?thrombocytosis together?

What type of systemic disease What type of systemic disease can be considered as a final can be considered as a final

diagnose?diagnose?

AMYLOIDOSISAMYLOIDOSIS

systemicsystemic topictopic senilesenile 14 different proteins-SAA, monoclonal 14 different proteins-SAA, monoclonal

lambda or kappa Ig light chains, mutant lambda or kappa Ig light chains, mutant transthyretin,cystatin, ANPtransthyretin,cystatin, ANP

AL (primary amyloidosis)AL (primary amyloidosis) monoclonal lambda or kappa Ig light chains monoclonal lambda or kappa Ig light chains

produced by a clonal plasma-cell dyscrasisproduced by a clonal plasma-cell dyscrasis ATTR (familial)ATTR (familial)

mutant transthyretinmutant transthyretin AA (secondary)AA (secondary)

amyloid A protein produce in response to a amyloid A protein produce in response to a chronic inflammatoy statechronic inflammatoy state

Anatomical diagnosis:Anatomical diagnosis:

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

AL AMYLOID

Heart failure Autonomic nervous system involvement

Peripheral nervoussystem involvement

Hepatomegaly

Splenomegaly

Nephrotic syndrome

Macroglossiahoarsenes

Hypofunctionof adrenal glandshypothyreosis

Anemia

Thrombocytosis

Carpal tunnel sy