M2Prof. Dr. S Sundar’s UnitCase Presentation

A case of QuadriparesisPresented by Dr.Deepu Sebin

Shabana , 28 year old female. Housewife from Washermanpet Patient being discharged from Govt. RSRM

hospital after Rx for 20 daysand received in the ward as case of

Clinical History in brief

She was an apparently normal ,except for her thin built .

First complaint started 1.5 years back as gradually progressing weakness of all four limbs .

For which she was treated in a local Hospital with Drugs and IV injections.

The weakness lasted for 2 weeks and she gradually recovered with treatment.

She was not on any long term drugs.

No records were available with the patient except for a nerve conduction study report which says :

Nerve conduction study suggestive of demyelinating radiculopathy (Motor neuronopathySensory conduction velocity normal.

She was symptom free since this first onset of weakness and conceived for the second time.

Antenatal period was uneventful

However on day 2 pospartum she started experiencing some weakness of her limbs and body

At presentation

Complains of weakness of both upper and lower limbs, progressing over 2 days

In upper limbs She has difficulty in mixing food, holding objects, also difficulty is

raising arm overhead, combing etc In lower limb

Difficulty in gripping chappals, Climbing stairs and sitting up from squatting positions ( All simultaneously)

She was confined to bed because of the weakness. History of difficulty in turning side to side in bed, history of

difficulty in lifting the neck + No higher mental function defects in history No history suggestive of cranial nerve involvement No sensory, bowel or bladder involvement Patient complained of breathing difficulty. Present even at rest

, no orthopnea or PND No h/o of fever or fever preceding the illness

Past H/o Similar illness 1.5 years back, probably treated

as Demyelinating disease No h/o PTB,CAD,DM,SHT

Personal history In Lactation amenorrhea Mixed diet

Family History Nil Specific

Clinical Examination

Patient is thinly built and poorly nourished Conscious, Oriented, Mod

dehydrated, Afebrile Dyspneic , Tachypneic

PR = 110/min BP = 110/70 Resp Rate: 36/min

General Examination No pallor, Icterus, cynosis, cubbing, LNE,

pedal odema, Thyroid - Normal

CVS Normal

RS – Normal

P/A Normal

CNS HMF – Normal CrN – Normal Spinomotor

▪ Bulk – ▪ Tone- decrease b/l▪ Power

▪ UL B/L Proximal 4-/5 Distal 4-/5

▪ LL B/L Proximal 3/5 Distal 3/5

Reflexes BJ + + TJ + + SJ + - KJ ++ ++ AJ + +

Superficial refexes present B/L Plantar flexor B/L

Sensory examination – Normal Cerebellum – Normal Skull & Spine -Normal No signs of meningeal irritation

ECG

CBC Hb-10.6 g/dl TC – 8600 DC – P64L39 ESR -16mm/hr Platelet – 1.4 lakhs

RFT B.Urea – 34 mg/dl S. Creatinine – 0.8

mg/dl RBS – 110mg/dl

S. electrolytes S.Na+ – 136 mEq S.K+ - 1.8 mEq

LFT – Normal

Urine Routine - Normal

Diagnosis : Hypokalemic Paralysis (? Periodic Paralysis )

Chest Xray - normal

Inj. KCL 40 meq TID was initiaited , since patient was not tolerating oral KCL (Which was later changed to oral KCL)

From next day onwards patient started showing improvement in power.

Not dyspneic or tachypneic anymore

T3- 179 (60-200) T4- 15 (4.5-12.0) TSH – 0.02 (0.30 – 5.5)

Thyrotoxic Periodic Paralysis

Spot Urine K+ - 48mEq/L **Low urine potassium (<20 mEq/L) suggests poor intake,

a shift into the intracellular space, or gastrointestinal loss. High urine potassium (>40 mEq/L) suggests renal loss.

ABG – Compensated Metabolic Acidosis + Respiratory alkalosis. AG normal

pH- 7.32 Pco2 – 22 HCO3- 14.0 Cl - 108 Na+ - 136 K+ - 1.4

Repeat investigations after stopping K+ supplimentation for 48 hours S. K+ - 2.8 S.Na+ - 133 S.Ca++ -10.8 S.Mg++ - 2.0 Spot Urine K + - 40 Spot Urine Na+ - 34 Spot Urine Cl- - 30 Spot Urine Creatinine – 15.5

Repeat ABG

pH 7.31 Bicarbonate - 14 mmol/1, PCO2 – 24mmHG Na+ - 133.2 mmol/l K+ - 2.9 mmol/l Cl- - 109 mmol/l Anion gap 14 mmol/1

Non anion gap metabolic acidosis, with respiratory compensation

24 hour Urine K+ - 119 meq/24 hr

***less than 20 mEq/24-hour urine specimen suggests appropriate renal conservation of potassium, while values above that indicate some degree of renal wasting.

Urine pH 7.00 7.2 7.0 Urine anion gap – positive Urine [ Na+K – Cl ] = [40+34-30] = +ve

Hypokalemia, Renal K+ loss, Non anionic metabolic acidosis, Normal GFR, Persistently high Urine pH, Positive Urine anion gap.

Diagnosis – Type 1 RTA

S.Ca++ - 10.4 mg/dl S.Mg++ - 2.0 mg/dl 24 hour Urine Ca++ -3.6 meq/24hr Thyroid antibodies – Not done Peripheral smear - Normal Chest, Xray KUB – Normal USG Abdomen – Normal. Kidneys normal

in size and echotexture. No evidence of calculi

MRI Brain with spine screening - normal

ANA – positive 1:100 speckled pattern

ds DNA – Negative Anti SSa– positive Anti SSb – negative RA factor – negative Schrimmers test at opthalmology

dept - 4 mm +ve

On further enquiry

History of dry mouth > 3months. History using water to swallow food +

History of dryness of eyes. No history sand / gritty feeling in the eyes

No arthralgia, no rash, no photosensitivity, no oral ulcers.

No history of palpitations, anxiety, heat intolerance or wt loss.

Final Diagnosis

Hypokalemic Periodic Paralysis Renal Tubular Acidosis Type 1 Probable Sjogren Syndrome Hyperthyroidism

On treatment with T. Carbimazole 5mg 2-2-2 Syp KCl 15 ml TID Bicarb Powder 3 sachets/day To review for Rpt electrolytes, ABG and further

evaluation for Sjogren Syndrome (Lip Biopsy).

THYROTOXICOSIS AND RENAL TUBULAR ACIDOSIS PRESENTING AS

HYPOKALAEMIC PARALYSIS C. C. SZETO, C. C. CHOW, K. Y. LI,

T. C. KO, V. T. F. YEUNG and C. S. COCKRAM

Department of Medicine, Prince of Wales Hospital, The Chinese University of Hong

Hypokalemic Paralysis : which is which

Atals of Rhuematology

Q

What is causing the periodic paralysis, Hyperthyroidism or Renal Tubular Acidosis or both ?

Why there were no symptoms of hyperthyroidism in this patient ?

Why the initial nerve conduction study showed Motor Demyelination ?

What awaits the patient ?

The normal renal response to acidemia (Acid Load) is to reabsorb all of the filtered bicarbonate in PCT and to increase hydrogen excretion (DT) primarily by enhancing the excretion of ammonium ions in the urine in Distal Tubules.

RTA

Normal Renal FunctionProximal Tubule

Reabsorption:

• HCO3- (90%) – carbonic anhydrase• calcium

• glucose

• Amino acids

• NaCl, water

Distal Tubule• Na+ reabsorbed

• H+ (NH4+ or phosphate salts) excreted• molar competition between H+ and K+

• Aldosterone

Normal Renal FunctionProximal Tubule

Reabsorption:

• HCO3- (90%) – carbonic anhydrase• calcium

• glucose

• Amino acids

• NaCl, water

Distal Tubule• Na+ reabsorbed

• H+ (NH4+ or phosphate salts) excreted• molar competition between H+ and K+

• Aldosterone

Type 2 RTAType 1 RTA

Type 4 RTA

1 IDHS[Type 1 impared distal hydrogen secretion]

2 IPBR[Type 2 Impared proximal bicarb reabsorption]

When to suspect ?

Hypo / Hyperkalemia Non Anion Gap Hyperchloremic

Metabolic Acidosis with Normal

GFR

Types of RTA

Distal or type 1 RTA

Proximal or type 2 RTA

Hypoaldosteronism or type 4 RTA

What happened to Type3 RTA ? Although initially used to describe a transiently severe

form of type 1 RTA in infants, the term type 3 RTA is now most often applied to a rare autosomal recessive syndrome (resulting from carbonic anhydrase II deficiency)

Type 1 RTA - DISTAL

Distal (type 1) RTA is Reduction in net secretion of H+ therefore

ammonium secretion in the collecting tubules.

The impairment in hydrogen ion secretion is manifested as an abnormally high (greater than 5.5) urine pH during systemic acidosis.

Decreased proton pump (H-ATPase) activity Increased luminal membrane permeability with backleak of hydrogen ions Diminished distal tubular sodium reabsorption which reduces the electrical

gradient for proton secretion

excreted

HCO3-

Distal RTA or RTA type 1 Acidification defect

H+

K+

Cl-

1 IDHS

Type 1 RTA - DISTAL

Distal RTA It is often associated with hypercalciuria due to the effects of chronic acidosis on both bone resorption and the renal tubular reabsorption of calcium.

Hypercalciuria contributes to the development of nephrolithiasis and nephrocalcinosis.

Major causes of type I (distal) renal tubular acidosis

Primary Idiopathic, sporadic ,Familial

Secondary Sjögren's syndrome Hypercalciuria Rheumatoid arthritis Hyperglobulinemia Ifosfamide , Amphotericin B Cirrhosis Systemic lupus erythematosus (may be hyperkalemic) Sickle cell anemia (may be hyperkalemic) Obstructive uropathy (may be hyperkalemic) Lithium carbonate Renal transplantation

Type 2 RTA - PROXIMAL

Proximal (type 2) RTA may occasionally present as an isolated defect, but is more commonly associated with generalized proximal tubular dysfunction called the Fanconi syndrome.

In addition to bicarbonaturia, generalized proximal dysfunction may be associated with one or more of the following: glucosuria, phosphaturia, uricosuria, aminoaciduria, and tubular proteinuria.

80% reabsorbed

15% reabsorbed

5% excreted

HCO3

HCO3

HCO3

HCO3

100%

Normal renal tubular function

30% reabsorbed

15% reabsorbed

HCO3

HCO3

HCO3

25% HCO3-

100%

K+

Proximal RTA or RTA type 2

Cl-Decreased proximal tubule efficiency

2 IPBR

Major causes of type 2 (proximal) renal tubular acidosis with or without the Fanconi syndrome

Primary disorders -Idiopathic, sporadic Familial disorders Cystinosis Tyrosinemia Hereditary fructose intolerance Galactosemia Glycogen storage disease (type I) Wilson's disease Acquired disorders Multiple myeloma Ifosfamide Carbonic anhydrase inhibitors Amyloidosis Heavy metals Vitamin D deficiency Renal transplantation Paroxysmal nocturnal hemoglobinuria

Type 4 RTA

End organ target failure or low aldosterone: Lost of sodium – hyponatremia Retention or decreased excretion of

potassium - hyperkalemia Absorption of chloride –

hyperchloremia Decreased excretion of acids –

metabolic acidosis Loss of fluid - dehydration

Adolsterone

Water

K+

Na

Na+

H+

Cl-RTA IV:

Hypoaldosteronism or pseudohypoaldosteronism

H20

Aldosterone deficiency Primary Primary adrenal insufficiency Congenital adrenal hyperplasia, particularly 21-hydroxylase deficiency Isolated aldosterone synthase deficiency Heparin and low molecular weight heparin Hyporeninemic hypoaldosteronism Renal disease, most often diabetic nephropathy Volume expansion, as in acute glomerulonephritis Angiotensin converting enzyme inhibitors , Nonsteroidal

antiinflammatory drugs ,Cyclosporine H HIV infection Some cases of obstructive uropathy

Aldosterone resistance Drugs which close the collecting tubule sodium channel Amiloride Spironolactone ,Triamterene ,Trimethoprim (usually in high

doses) ,Pentamidine Tubulointerstitial disease Pseudohypoaldosteronism Distal chloride shunt

Lab Diagnosis of Type 1 & 2 RTA

Hypokalemia

ABG showing non anionic gap metabolic acidosis

24 hour Urine K+ > 40 showing kidney are losing K+ inspite of low serum K+ *Renal Loss*

Urine pH

Patients without RTA and normal renal function, the urine pH should be below 5.0 to 5.3 when metabolic acidosis is present.

Type : 1 In most cases of type 1 RTA, the urine pH is

persistently above 5.3, reflecting the primary defect in distal acidification.

Type : 2 Varies

Urine Ammonium Excretion

Urine Anion Gap is Urine Na+K – Cl Type 1 RTA – IDHS – positive Anion

Gap

excreted

HCO3-

Distal RTA or RTA type 1IDHS

Acidification defect

H+

As NH4

Along with

Cl-

K+

Cl-

Urine anion gap = [Na+] + [K+] – [Cl-]

Urine Anion Gap

The urine AG has a negative value in most patients with a normal AG metabolic acidosis due to the appropriate increase in urinary ammonium in an attempt to excrete the excess acid .

Ammonium is an unmeasured cation; as a result, an increase in its excretion as NH4Cl will lead to a rise in the urine Cl concentration and a negative urine AG, usually ranging from -20 to -50 meq/L.

In comparison, patients with renal failure, type 1 (distal) renal tubular acidosis (RTA), or hypoaldosteronism (type 4 RTA) are unable to excrete ammonium normally. As a result, the urine AG will have a positive value . ( due to decresed Cl- excretion into urine)

Fractional Excretion of Bicarbonate

The diagnosis of type 2 RTA can be established simply by raising the plasma bicarbonate concentration toward normal (18 to 20 meq/L) with an intravenous infusion of sodium bicarbonate at a rate of 0.5 to 1.0 meq/kg per hour

The urine pH, even if initially acid, will rise rapidly once the reabsorptive threshold for bicarbonate is exceeded.

As a result, the urine pH will be above 7.5 and the fractional excretion of bicarbonate (FEHCO3) will exceed 15 to 20 percent.

PCT Bicarb reabsorbing defect

Only 30% reabsorbed

More bicarb in urine (FE%)

pH becomes high

15% reabsorbed

HCO3

HCO3

HCO3

25% HCO3-

K+

Proximal RTA or RTA type 2

Cl-

2 IPBR

Give more Bicarb

                  UHCO3   x   PCr     FEHCO3    =    — — — — — — — — — — —

    x    100                               PHCO3   x   UCr

In type 2 RTA

urine pH will be above 7.5 and the fractional excretion of bicarbonat (FEHCO3) will exceed 15 to 20 percent

Urine pH 7.00 7.2 7.0

Urine anion gap – positive Urine [ Na+K – Cl ] = [40+34-30] = +ve

24 hr urine K+ 119 (high)

Hypokalemia, Reanl K+ loss, Non anionic metabolic acidosis, Normal GFR, Persistently high Urine pH, Postive Urine anion gap.

Diagnosis – Type 1 RTA

Treatment – Type 1 RTA

Bicarbonate wasting is negligible in adults who can generally be treated with 1 to 2 meq/kg of sodium bicarbonate

Bicarbonate therapy helps in allowing normal growth to resume, minimizing new stone formation and nephrocalcinosis, decreasing the risk of osteopenia;, lowering inappropriate urinary potassium losses.

Potassium citrate, alone or with sodium citrate (Polycitra™ ), is indicated for persistent hypokalemia or for calcium stone disease

Treatment – Type 1 RTA

Phosphate and vitamin D supplementation may be necessary to normalize the plasma phosphate concentration.

Treatment is more difficultBecause bicarbonate give will be lost

from PCT

Thus, 10 to 15 meq of alkali/kg may be required per day to stay ahead of urinary losses .

Features of the RTA Syndromes

Feature Type 1 Type 2 Type 4

Nephro-lithiasis

present absent Absent

Nephro- calcinosis

present absent Absent

Osteo-malacia

present present Absent

Growth failure

+++ ++ +++

Hypokalemic muscle weakness

++ + -

Alkali therapy

Low dose (2 –4 meq/kg)

High dose ( 2-14 meq/kg)

Low dose ( 2-3 meq/kg)

Response to therapy

good fair fair

Features of the RTA SyndromesFeature Type 1 Type 2 Type IV

Plasma HCO3

Variable, may be <10 meq/L

14- 18 meq/L

15-29 meq/L

Plasma Cl- increased Increased Increased

Plasma K+ Mildly to severely decreased

Mildly decreased

Mildly to severely decreased

Plasma anion gap

Normal Normal Normal

GFR Normal or slightly decreased

Normal of slightly decreased

Normal to moderately decreased

Fractional Excretion of HCO3

<5% > 15% <5%

Urine pH during acidosis

>6.0 </= 5.5 </= 5.5

Thank you

1 IDHS2 IPBR

In patients with type 1 RTA, the urine anion gap is

positive, in low urine NH4+ levels. In patients with a normal anion gap

metabolic acidosis and hypokalemia due to diarrhea, the urine anion gap is negative because urine ammonium excretion rises appropriately in response to the acidosis.

 A normal AG acidosis is characterized by a lowered bicarbonate concentration, which (in the presence of a normal sodium concentration) is counterbalanced by an equivalent increase in plasma chloride concentration. For this reason, it is also known as hyperchloremic metabolic acidosis.

The diagnosis of proximal RTA is made by measurement of the urine pH and fractional bicarbonate excretion during a bicarbonate infusion. The hallmark is a urine pH above 7.5 and the appearance of more than 15 percent of the filtered bicarbonate in the urine when the serum bicarbonate concentration is raised to a normal level.

Urine anion gap (UAG)

Urine anion gap = [Na+] + [K+] – [Cl-]

Normal: zero or positive Metabolic acidosis: NH4+ excretion increases (which is

excreted with Cl-) if renal acidification is intact

GI causes: “neGUTive” UAG Impaired renal acid excretion (RTA): positive or zero

Often not necessary b/c clinically obvious (diarrhea)