R3 case conference

報告者 :楊仁星指導老師 :方基存醫師報告日期 :2011-11-2

Index

Case presentation Discussion Back to the case

Case Presentation

Patient’s Profiles

Name: 陳 x 羽 Gender: female Age: 58 years Ethnic: Taiwanese Marriage: married Occupation: Waitress, School janitor, 有線電視服

務員 Chart number: 39037xxx Date of admission: 2011-9-26

Chief complaint

General weakness for 4 days

Present Illness-I

The patient had weakness of bilateral lower limbs for several days

4 days before admission, the weakness was progressed to general weakness.

She received injection of unknown substance (may be analgestic) at LMD.

Present Illness-II

After injection, the weakness became worsen and then the patient couldn’t walk and stand.

The associated symptoms included palpitation.

She came to our ER for help

Present Illness-III

She denied fever, chest pain, chest tightness, cold sweating, dyspnea, dizzness, nausea, vomiting, diarrhea, anorexia, tarry or bloody stool, frequency, urgency and flank pain.

Past History:

Diabetes mellitus for half year without control

Denied hypertension, heart disease, HBV, HCV and operation history

Personal history:

Allergy: no known allergy Alcohol: denied Smoking: denid Betelnut: denied Medication history: Chinese Medicine ( 大豆

類黃酮 , 保護關節藥 )

Family History:

DM

Physical Examination-I

Vital sign: BT: 36 , PR:62/min, RR: 18/min, BP: 121/80 mmHg℃ General appearance: fair looking Consciousness: alert, E4V5M6 HEENT: sclera: not icteric,

conjunctiva: not pale Neck: supple, JVE (-/-), LAP (-/-) Chest: bilateral symmetric expansion

bilateral breathing sound: clear Heart: regular heart beat without murmur

Physical Examination-II Abdomen: flat no superficial vein engorgement no spider angioma normoactive bowel sound no tenderness, no rebound pain no Murphy’s sign liver and spleen not palpable no shifting dullness Back: no knocking pain over bilateral flank pain Extremities: no pitting edema at bilateral lower limbs Skin: no petechiae or ecchymoses no skin rash

EKG at ER

CXR at ER

Lab data-I9/25 CBC/DC

WBC (/uL) 8400

RBC 4.28 x 106

Hb (g/dL) 12.6

Hct (%) 36

MCV (fL) 84.1

MCH (pg/Cell) 29.4

MCHC (gHb/dL) 35

Platelets (/uL) 220 x 103

Seg (%) 82

Lymphocyte (%) 12

Monocyte (%) 6

Eosinophil (%) 0

Basophil (%) 0

9/25 Biochemistry

BUN (mg/dL) 12.9

Cr. (mg/dL) 0.74

Na (mEq/L) 141

K (mEq/L) 1.4

Ca (mEq/L) 9.3

ALT (U/L) 16

Lab data-II

Impression

Hypokalemia periodic paralysis Diabetes mellitus

Clinical course-I

Clinical course-II

Other blood tests during hospitalization

Clinical course-III

Urine anion gap:

56+14.1-62 = 7.9

Clinical course-III kidney echo on 9/30

Clinical course-IV kidney echo on 9/30

Clinical course-Vkidney echo on 9/30

Left Kidney Length: 10.7 cm

Right Kidney Length: 11.8 cm

Impression:1. Right renal stone (0.7c

m)

2. Bilateral renal calcification spots

3. Parenchymal renal disease

Clinical course-IV

Final diagnosis

Type I renal tubular acidosis, suspect autoimmune disease related

Renal stones Type II diabetes mellitus, under diet

control

Discussion

Renal tubular acidosis

Renal tubular acidosis

A systemic hyperchloremic and normal anion gap acidosis with relatively normal glomerular filtration rate

Results from either the net retention of hydrogen chloride or net loss of sodium bicarbonate

Three major subgroups of RTA• Distal or type 1 RTA

• Proximal or type 2 RTA

• Hypoaldosteronism or type 4 RTA

Renal tubular acidosis-distal RTA (type 1)

Failure of distal nephron and collecting duct to secret hydrogen ion

Failure to reabsorb filtered bicarbonate that was not reabsorbed in proximal tubule

Failure of titration of phosphate buffer and decreased exc

retion of NH4+ Precise nature of defect is not known.

dRTA (Type I)

dRTA (Type I)- Etiology

dRTA (Type 1)- Clinical features muscle weakness Hyperventilation Acute acidosis Hypokalemia Inability to acidify the urine to a pH of less than 5.3 70% have either nephrocalcinosis (very rarely a feat

ure of other types) or calcium containing renal calculi Rickets and growth stunting are frequent features in

childhood cases. ± osteomalacia in adults

Renal tubular acidosis-proximal RTA (type 2)

Proximal tubule reabsorption of approximaly 80~90%

Type 2 RTA:

• an impariment of HCO3- reabsorption in the pr

oximal tubule

• Decreased renal HCO3- threshold

• Distal acidifcation mechanisms are intact

• May lower urine pH below 5.5

pRTA ( Type 2)

pRTA ( Type 2): Etiology

pRTA ( Type 2): Clinical feature General weakness Metabolic acidosis Hypokalemia proximal myopathy, osteomalacia or rick

ets Normal urinary acidification Nephrocalcinosis and renal calculi are vir

tually never present

Renal tubular acidosis-type 4

Type 4 RTA is not actually a tubular disorder reduction in proximal tubular ammonium excret

ion, which is secondary to hypoaldosteronism or pseudohypoaldosteronism, and results in a decrease in urine buffering capacity.

Presentation: hyperkalemia and normal urinary acidification

Nephrocalcinosis and Urolithiasis are absent in type 4

Hyperkalemic RTA (Type 4): Etiology

Renal tubular acidosis

Sjogren’s syndrome

Sjögren's syndrome A chronic autoimmune disease, affecting mainl

y the exocrine glands. Prevalence: 0.3%~0.6% Female:male: 9:1 Can affect extraglandular, such as involvement

of the musculoskeletal, pulmonary, GI, hepatobiliary, hematologic, vascular, dermatologic, renal and nervous systems.

Sjögren's syndrome-Classification Primary SS: occur alone Secondary SS: association with another

defined autoimmune disease (eg, SLE, RA, or scleroderma)

Sjögren's syndrome-Symptoms Two main symptoms: dry eye and dry mouth Other:

• Joint pain, swelling and stiffness

• Swollen salivary gland

• Skin rashes or dry skin

• Vaginal dryness

• Persistent dry cough

• Prolonged fatigue

Diagnosis Criteria 2002 American-European consensus Classification Criteria,

required four of the following

Renal involvement in primary Sjogren’s syndrome

Sjogren’s syndrome is an autoimmune disorder and the target organs are the exocrine glands, especialy the lacrimal and salivary

Kidney involvement is a frequent extraglandular manifestation of primary Sjogren’s syndrome

30~40% of Sjogren’s syndrome patients have symptomatic and asymptomatic renal involvment.

The understanding of the clinical presentation of renal involvement in primary Sjogren’s syndrome is based on case reports and small retrospective cohorts.

Clinical and laboratory features

Clinical and laboratory features

Patient with Sjogren’s syndrome and RTA tend to present hypokalemic periodic paralysis (HPP)

20 cases of SS-associated HPP reported between 1966~2008

Pathogenesis The pathogenesis of the RTA in Sjogren syndrome is u

nclear Interstitial infiltrate composed of lymphocytes and plas

ma cells, with secondary invasion of the tubular membrane and lining epithelium -> tubular cell architecture disrupt -> secretion of distal tubule defect

Absence of intact H+-ATPase in intercalated cell -> H+ ion secretion defect

Hypergammaglobulinemia cause distal renal tubular dysfunction

Anti-carbonic anhydrase II antibiodies

Carbonic anhydrases (CAs) Key enzymes in the regulation of acid-ba

se balance in both physiological and pathological status

Autoantibodies to carbonic anhydrase II (CA II) are increased in renal tubular acidosis with Sjogren’s syndrome ( in the past study )

Several new CA isoenzymes (1~13) have been discovered in recent.

Recent study, published in Rheumatogy 2011 revealed that none of the anti-CA antibiotics was associated with presence of RTA or proteinuria or urinary α1

m excretion in patients with PSS.

Carbonic anhydrases (CAs)

Title: Novel carbonic anhydrase autoantibodies and renal manifestations in patient with primary Sjogren’s syndrome

Methods: • examined anti-CA II antibodies as well as ant

i-CA I, VI, VII and XIII antibodies by ELISA test in 74 pSS patients (F:M : 70:2) and 56 patients with Sicca symptoms (F:M : 46:10)

Title: Novel carbonic anhydrase autoantibodies and renal manifestations in patient with primary Sjogren’s syndrome

Result:• The levels of anti-CA I,

II, VI and VII antibiotics differed significantly between two groups

Title: Novel carbonic anhydrase autoantibodies and renal manifestations in patient with primary Sjogren’s syndrome

Result:• 33 patients (45%) of pSS had proteinuria and

31% pSS had overt or latent dRTA.

• None of the studied anti-CA antibodies ( anti-CA I, II, VI, VII and XIII antibodies) was associated with dRTA, presence of protienuria.

• Urinary pH was significantly associated with levels of anti-CA II, VI and XIII antibodies.

Title: Novel carbonic anhydrase autoantibodies and renal manifestations in patient with primary Sjogren’s syndrome

Histological The most presentation is tubulo-interstitial nephritis (71%)

1. lymphocytic interstitial infiltrate, 2. interstitial fibrosis 3. tubular atrophy

Histological

Patients had chronic glomerulonephritis is rare

The most common types are membranoproliferative glomerulonephritis and global glomerulosclerosis

Proliferative GN Minimal change GN Membranous nephropathy

MPGN Cryoglobulinemic GN

Representative microphotographs of the diverse glomerular pathology seen in PSS

Histological

Histological Proliferative glomerulonephritis with humps an

d monotypic IgG1-kappa deposits had reported ( NDT,2010/9: Non-Randall proliferative glomerulonephritis with humps and monotypic IgG deposits in primary Sjogren’s syndrome, first case report)

• 50-year-old female• Has experienced asymmetric joint pain and swelling a

ssociated with relapsing episodes of fever• Has mild proteinuria, intermittent microscopic hematuri

a, normal renal function• Negative cryoglobulinemia, anti-DsDNA and ANCA• Positive ANA, SSA, SSB, RF and anti-phospholipid an

tibodies• Total serum protein elevated with hypergammaglobuli

nemia

Immunofluorescence showed abundant subepithelial and mesangial deposits staining brightly for IgG1, C3 and kappa light chain

Absence of organization of the deposits appearing as humps by light microscopy.

Immunofluorescence showed abundant subepithelial and mesangial deposits staining brightly for IgG1, C3 and kappa light chain

Treatment:

Potassium replacement therapy Consider steroids in case of RTA

associated with SS

Back to the case

Our patient’s characteristics:

Progressive weakness Hypokalemic Normal anion gap metabolic acidosis Positive urine anion gap Positive ANA, anti-SSA, anti-SSB Negative for dsDNA Normal RF, C3, C4

Suspect the patient presented with symptoms of hypokalemic periodic paralysis and distal RTA is due to autoimmune disease, especially like Sjogren’s syndrome

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