Physiological basis

K+:< ICF: 150 meq/L

       ECF: 3.5 -5 meq/L

• Sodium is the major ECF cation (sodium value 140 mEq/L ECF vs 25 mEg/L intracellular).

Total body k+- 3500meq

• Total body sodium is about 5,000 mEq in a normal adult person.
• 85-90% sodium is extracellular.

K+ -98% Intracellular

       2%. Extracellular

• Sodium is responsible for more than 90% of total osmolality of extracellular fluid.
• Major function of sodium is to maintain ECF volume and therefore maintain blood pressure.
• ECF volume is reflection of total body sodium content (amount).
• Daily requirement of sodium is about 100 mEq or 6 gm of sodium chloride.

K+ requirement is 50-80 meq day

• Excess salt is excreted chiefly by kidney. Loss of sodium in sweat is poor (30-65 mEq/L).]

Response to sodium deficit

• Deficiency of sodium in body will lead to hypovolemia and activates Angiotensin-Il and Aldosterone.
• By acting on the kidney, angiotensin-Il helps to increase sodium absorption at the proximal tubules and aldosterone at the collecting duct.
• In a state of sodium deficit, absorption of Na under aldosterone control is so perfect that almost no urinary Na loss occurs. So by almost complete absorption of Na kidney helps to prevent sodium loss.

Renal priority

• To reclaim sodium under aldosterone influence, initially potassium and it needed later on Htis lost in the urine.
• Due to body’s priority to reclaim Na > H > K, during abnormal loss of all electrolytes (like in diarrhoea) hypokalemia is the commonest abnormality.

Response to sodium excess

• When there is excess amount (content) of sodium it will lead to increased ECF volume, which will lead to decreased Angiotensin-ll, Aldosterone and increase in ANP.
• Decreased angiotensin-ll and aldosterone level will lead to decreased renal reabsorption of sodium.
• Increased ANP will lead to natriuresis and diuresis.
• Hence net result is increased urinary excretion of sodium. Thus extra sodium will be lost.

HYPERNATREMIA

Hypernatremia is defined as plasma sodium concentration greater than 145 mEg/L. Hypernatremia is a less frequent disorder and indicates either lack of water or primary sodium gain.

HYPERNATREMIA IS USUALLY DUE TO WATER DEFICIT AND NOT SODIUM OVERLOAD.

The thirst mechanism is very effective in preventing hypernatremia. So hypernatremia usually does not occur unless there is non-availability of water, impaired thirst or comatose-confused patient unable to drink water.Therefore, hypernatremia is seen chiefly in very young, very old and very sick or debilitated patients. Pure water deficit leading to hypernatremia is called dehydration.

ETIOLOGY

Common causes of hypernatremia are summarized in Table No. 3.4.

Etiology of hypernatremia

Excess water loss.

A.Insensible loss

     Dermal : Heat exposure, severe burns, severe exercise.

     Respiratory : Patient on mechanical ventilator.

B.Renal loss :

     Diabetes Insipidus (central or nephrogenic)

     Excessive diuretics, uncontrolled DM

C.Gastrointestinal losses

     Osmotic diarrhoea.

Water deficit due to impaired thirst.

• Primary hypodypsia, confused or comatose conditions.

Sodium retention.

• Excessive I.V. hypertonic NaCI or NaHCO3

CLINICAL FEATURES

Clinical features of hypernatremia are primarily neurological and they depend upon the rapidity of onset, its duration and its magnitude.This is the only state in which dry sticky mucous membrane is characteristic and body temperature is generally elevated. Major neurological symptoms include nausea, muscular weakness, altered mental status, neuromuscular irritability, focal neurological deficit and occasionally coma or seizures.

In severe acute hypernatremia brain shrinkage may be substantial,exerting traction on the venous sinuses. It can cause intracerebral and subarachnoid hemorrhage which may produce irreversible neurological deficit or even death. The patient may also complain of polyuria or excessive thirst. The signs and symptoms of volume depletion are often present in patient with history of excessive sweating, diarrhea or osmotic diuresis.

Even though there is equal volume of fluid losses, why the patients with hypertonic dehydration are haemodynamically more stable than the patients with isotonic volume depletion

Pure water loss leads to dehydration with hypernatremia (hypertonic dehydration), whereas proportionate combined loss of water and salt in isotonic volume depletion leads to hypovolemia and has normal serum sodium.

In isotonic volume depletion, fluid loss leads to reduction only in ECF volume (and therefore early reduction in intravascular volume) leading to hypotension and reduction in tissue perfusion. While in dehydration due to pure water depletion there is proportionate reduction in total body water (2/3 from ICF and 1/3 from ECF). As ECF volume depletion land therefore intravascular volume depletion, which is 1/4 of ECF) is much less, clinical features are lesser in pure water depletion

DIAGNOSIS

Complete history and examination may provide the clue for etiology of hypernatremia. Renal and glycaemic status, urinary volume, osmolality and glycosuria and response to vasopressin in diabetes insipidus are useful for etiological diagnosis of hypernatremia

TREATMENT

The therapeutic goals are :

1.To stop ongoing fluid loss by treating the underlying causes.

2.To correct water deficit.

Two important factors to decide treatment plan are

i.ECF volume status and

il.Rate of development of hypernatremia.

The important treatment aspects are

• To diagnose and treat specitic etiology (i.e. treating diabetes insipidus,DM, hypokalemia, hypercalcemia etc. and stopping diarrhoea)
• Fluid deficit : The amount of water required to correct the deficit can be calculated from the following equation.

               Water deficit = Plasma Na-140 × 0.6 x body weight in kg.

                                                140

• In addition to water deficit, ongoing and insensible loss needs to be replaced. Correct the total fluid deficit over 48-72 hours.
• Rate of correction : In acute hypernatremia the water deficit can be replaced relatively rapidly, without increasing the risk of cerebral edema. In acute hypernatremia targeted rate of correction of hypernatremia is 1 mEq/L/hr. Rapid correction of chronic hypernatremia is dangerous. It may lead to neurological problems due to development of cerebral edema. Safe rate of correction is reduction of serum sodium by 1 mEq/every 2 hours or 10 mEq/L over first 24 hours.
• Goal of treatment : The goal is to reduce serum Na concentration to 145 mEg/L.
• Deterioration of neurological symptoms after initial improvement suggests the development of cerebral edema and requires temporary discontinuation of water replacement
• Treatment of hypernatremia is water. The safest route of administration of water is by mouth or via a nasogastric tube.
• Acute hypernatremia is treated vigorously with D-5% infusion.Large and rapid infusion of D-5% will lead to hyperglycemia and osmotic diuresis, which may aggravate hypernatremia. If required,hyperglycemia can be combated with insulin therapy.
• Hypernatremia with ECF volume contraction: If there is severe loss of ECF volume with hypotension and azotemia, isotonic saline is given initially until the ECF volume is restored. Subsequently water deficit can be replaced with water by mouth or I.V. 5%-dextrose or 0.45% NaCI.
• Sodium concentration of 0.9% NaCI (154 mEq/L) is greater than the normal serum sodium (140 mEq/L), but is generally lower than the serum sodium concentration in hypernatremia. So initial therapy with 0.9% Nacl,has an advantage of rapid correction of hypotension and avoiding unnecessary rapid fall of serum sodium.
• Method to calculate change in serum Na for given infusate : Change in serum Na concentration, for the infusion of one litre of appropriately selected I. V. fluid, can be calculated by formula mentioned below

Change in serum sodium concentration =

Infusate Na/L – Serum Na

Total body water (L) + 1

or

Infusate (Na + K)/L – Serum Na

Total body water (L) + 1

(For details of Na concentration of infusate and method to calculate total body water refer treatment of hyponatremia).

• Hypernatremia with increased ECF volume : In these patients hypernatremia is secondary to solute administration. The hypernatremia is acute and can be rapidly corrected. These patients are usually volume overloaded. A loop diuretic is administered along with water to facilitate sodium excretion. In patient with massive overload or renal failure dialysis may be necessary.

HYPONATREMIA

Hyponatremia is defined as plasma sodium less than 135 mEg/LHyponatremia is not uncommon in a hospitalized patient (incidence 1.5 to  2.5%), but is rarely seen in an ambulatory patient (if present, reflects a chronic disease status).

Serum sodium reflects the relative proportion of sodium and water.

Hyponatremia usually means water overload and not sodium deficit.

Hyponatremia can occur with normal, low or even high total body sodium.

So basically hyponatremia can be dilutional ( water excretion lesser than water intake and so needs fluid restriction as the most important treatment) or due to sodium loss (needs sodium and fluid supplementation).

• Hyponatremia usually means water retention

ETIOLOGY

Low serum Na leads to decreased serum osmolality, so true hyponatremia is characterized by hypoosmolality. ECF volume varies in hyponatremic patients, depending upon etiology. So etiology of hyponatremia is classified on basis of these two criteria, osmolality and ECF volume.

Pseudo hyponatremia (increase Lipids, increase Proteins, +increase Carbs)

• Normal osmolality: Hyperlipidaemia, Hyperproteinaemia
• High osmolality:Hyperglycaemia, Mannitol

Hyposmolar hyponatremia (true hyponatremia)

A.Hyponatremia with ECF volume depletion

Patient dehydrated reduction in total body sodium exceeds reduction in total body water)

1.Extra renal loss (Urinary sodium < 15 mEq/L)

Vomiting, diarrhea, peritonitis.

2.Renal loss (Urinary sodium > 20 mEq/L)

Excessive diuretics, salt losing nephropathy, diabetic

ketoacidosis, cerebral salt wasting syndrome.

B. Hyponatremia with hypervolemia, increased CF volume

Patient oedematous- Increase in total body water exceeds

increase in total body sodium)

Urinary sodium < 20 mEq/L : CHF, cirrhosis and nephrotic syndrome.

Urinary sodium > 20 mEq/L : Renal failure

C.Hyponatremia with normal ECF volume

(Patient normovolemic, increased total body water)

• SIADH, post operative pain, hypothyroidism, glucocorticoid deficiency, psychogenic polydypsia, drug induced.

CLINICAL FEATURES

The severity of symptoms depends upon the severity of hyponatremia and the rate at which the plasma sodium concentration is lowered. So acute and severe hyponatremia is symptomatic but chronic and mild hyponatremia is well tolerated. The very young and elderly patients are more symptomatic.

DIAGNOSIS

History and physical examination is often helpful in identifying hypovolemic hyponatremia (diarrhea, vomiting, burns, diuretics etc.)

Three important diagnostic tests are

 1. Plasma Osmolality

Low : True hyponatremia

Normal or elevated : Pseudohyponatremia or renal failure.

2. Urine Osmolality

< 100 mOsm/kg or specific gravity < 1.003, diluted urine suggest primary polydypsia with normal water excretion.

> 100 mOm/kg, other causes of hyponatremia in which water excretion is impaired.

3. Urine Sodium Concentration :

< 15 mEq/L effective volume depletion e.g. diarrhea, vomiting

> 20 mEq/L SIADH (normo volemia) or renal salt wasting (diuretics, renal disease or hypoaldosteronism)

 Hyponatremia is usually associated with low plasma osmolality. But if osmolality is normal or high, rule out pseudohyponatremia

 Normal plasma osmolality i2 275- 290 mOsm/kg.

Plasma= 2× Na +Glucose (mg/dI) + BUN (mg/dI)

Osmolality                     18                        2.8

• Associated hyperkalemia suggests renal insufficiency or adrenal insufficiency with hypoaldosteronism.
• Associated hypokalemia and metabolic alkalosis suggest vomitina or diuretic therapy.
• Diuretics induced hyponatremia is almost always due to thiazide diuretics. (Loop diuretics:Water diuresis > hyponatremia infrequent).

TREATMENT

Treatment of hyponatremia must be individualized considering etiology, rate of development (acute vs. chronic), severity and clinical signs and symptoms.dictum; hyponatremeia which davelops quickly, should be treated fast.Whereas hyponatremia, which develops slowly, should be corrected slowly.

Goal of therapy

1.To raise the plasma sodium concentration at a safe rate.

2.To replace sodium deficit or potassium deficit or both.

3.To correct underlying etiology.

In general hyponatremia is corrected acutely by giving sodium to patients who are volume depleted and by restricting water intake in patients who are normovolemic or oedematous.

Specific treatment

• Removal of the drugs responsible for hyponatremia:
• Thiazide Diuretics, Chlorpropamide or .V. Cyclophosphamide.
• Management of physical stress, (postoperative pain).
• Specific treatment for adrenal insufficiency, hypothyroidism, nephrotic syndrome, CHF, uncontrolled diabetes or ketoacidosis,salt losing nephropathy etc.

1. Hyponatremia with hypovolemia

These patients require fluid and salt supplementation which can be done with I.V, isotonic (0.9%) NaCI (or even oral salt containing water) at rate appropriate for the estimated volume depletion. Intake of simple water or I.V. fluid with low Na (0.45% NaCI, Isolyte-M, 5%-dextrose, etc.) should be restricted until the plasma sodium is within the normal range, because it will aggravate hyponatremia.

Diuretics induced hyponatremia is treated with saline with postassium supplementation (30-40 mEq/L).

2 Hyponatremia with hypervolemia (Oedematous state)

Therapy is difficult in oedematous state since sodium supplementation will worsen fluid overload. Such patients are treated with diuretics, salt restriction, fluid restriction (intake < urine output) and correction of potassium deficit in addition to the etiological treatment.

3.Hyponatremia with euvolemia

Hyponatremia with normal or high ECF volume has impaired water excretion with normal or high total body sodium. In such patients fluid restriction is the most important treatment. Adequate restriction of fluid intake will gradually increase serum sodium concentration.

Basic principles of correction of hyponatremia

Treatment of hyponatremia should balance the risk of hypotonicity due to hyponatremia and the risk of therapy.

• To treat or not to treat :

How rapidly hyponatremia should be corrected is a dilemma, Patients with severe hyponatremia (110-115 mEq/L) are at risk of developing severe and potentially irreversible neurological damage and sometimes even death. On the other hand, too rapid correction of severe hyponatremia can produce central pontine myelinosis or osmotic demyelination syndrome (ODS), which can cause substantial morbidity and mortality.

• When to treat,When not to treat :

A.Patient with seizures or other severe neurological symptoms due to hyponatremia needs prompt treatment. In this setting, risk of untreated hyponatremia and cerebral edema is greater than the potential harm of rapid correction. So rapid correction is indicated in acute (<48 hours) symptomatic or severe (serum Na < 120 mEq/L) hyponatremia.Ön the other hand, chronic (> 48 hrs) and mild hyponatremia, with minimal neurological symptoms are at little risk due to hyponatremia. However, these patients can develop demyelination following rapid correction. So there is no necessity to correct these patients rapidly and they should be treated using slower acting therapy such as fluid restriction. Pay particular attention to premenopausal women, elderly and young children as they are more symptomatic and need early treatment.

Chronic asymptomatic hyponatremia

• The targeted rate of plasma sodium should not be greater than 0.5 to 1.0 mEq/L/hour.
• Raise the plasma sodium by less than 10 to 12 mEq/L on the first day and less than 18 mEq/L over the first two days. As per recent recommendations a targeted rate of correction should not exceed 8 mEq/L on any day of treatment.
• If the rate of correction is faster or rise in serum sodium is > 25 mEq/48 hours or correction is made until normonatremia (serum sodium 140 mEq/L) is achieved there is high risk of central pontine myelinosis.

Acute hyponatremia with severe neurological symptoms

These patients require rapid correction of plasma Na with hypertonic saline. Initial rate of rise of Na concentration should be 1.5-2 mEq/L/hr for the first 3 to 4 hours or until the severe neurological symptoms improve. Besides this initial rapid correction rise in the plasma sodium concentration should not exceed 10-12 mEg in first 24 hours. Patient with seizures also require immediate anticonvulsant drug therapy and adequate ventilation.

How long to treat and when to stop acute correction of hyponatremia

A.Regardless of the initial rate of correction, chosen acute treatment should be interrupted once any of the three end points is reached

1) Patient’s symptoms are abolished.

2) A safe plasma sodium (generally 120-125 mEq/L) is achieved or

3.A total magnitude of correction of 20 mEq/L is achieved. It is necessary to correct hyponatremia accurately to a safer range,rather than correcting completely to normonatremia.

Fluid should be used to correct hyponatremia

• Aim of fluid infusion is to raise Na. by correcting Na delicit, so the infused fluid should contain higher Na concentration than desired or normal serum sodium concentration.
• 0 9% saline (154 mEQ/L Na) and 3% NaCl-hypertonic saline (513mEq/L Na) are the only two routinely used IV fluids which have higher Na concentration and therefore are used to correct hyponatremia. However, for the treatment of hyponatremia due to SIADH, infusion of 0.9% NaCI is inappropriate.
• When hyponatremia is associated with hypovolemia or in absence of fluid retention or edema, 0.9% saline is the preferred fluid.
• But when patient needs salt supplementation along with fluid restriction hypertonic saline is the preferred fluid (e.g. severe form of SIADH).

Monitor Na during treatment of hyponatremia

During treatment of hyponatremia, many other independent factors can modify the Na concentration (e.g. urinary and other losses of Na, addition of oral fluid intake etc.). So frequent monitoring of the serum sodium concentration (atleast at 4 to 6 hours interval initially), is necessary to ensure that the rate of correction is as desired and in order to make further adjustment in the amount and rate of fluid administration. Remember, in symptomatic/sick patients with hyponatremia, calculation of the requirement of Na containing IV. fluids for whole 24 hours and their infusion without proper monitoring and modification can be dangerous.

Limb ischemia is a severe blockage in the arteries of the lower extremities, which significantly reduces blood flow. Acute limb ischemia is a sudden and rapid decrease in lower limb blood flow. 

TYPES

• Acute limb ischmia
• Chronic limb ischemia
• Critical limb ischemia

Acute limb ischemia

• Acute limb ischemia is a sudden and rapid decrease in lower limb blood flow. 

Chronic limb ischemia

• Chronic limb ischaemia is peripheral arterial disease that results in a symptomatic reduced blood supply to the limbs.
• It is typically caused by atherosclerosis (rarely vasculitis) and will commonly affect the lower limbs (however the upper limbs and gluteals can also be affected)
• Chronic limb ischaemia is a common condition, ranging in severity across the population, associated with several cardiovascular risk factors
• Whilst a clinical diagnosis, it can be quantified by ABPI testing, following by angiogram imaging
• Surgical intervention can be offered if conservative management options fail or those presenting with critical limb ischaemia.

Critical limb ischemia

Critical limb ischaemia is the advanced form of chronic limb ischaemia.

It can be clinically defined in three ways:

• Ischaemic rest pain for greater than 2 weeks duration, requiring opiate analgesia
• Presence of ischaemic lesions or gangrene objectively attributable to the arterial occlusive disease.
• ABPI less than 0.5

There are three main stages of acute limb ischemia: 

• Stage 1: Viable
  • Limb is not immediately threatened
  • No sensory loss
  • No muscle weakness
  • Doppler signals of arteries and veins are audible
• Stage 2: Threatened 
  • Stage 2a: Marginally threatened 
    • Limb is salvageable if promptly treated
    • Minimal sensory loss (toes) or no sensory loss
    • No muscle weakness
    • Doppler signals of arteries are often inaudible; veins are audible
  • Stage 2b: Immediately threatened 
    • Limb is salvageable with immediate revascularization
    • Sensory loss is more than toes, associated with rest pain
    • Mild to moderate muscle weakness
    • Doppler signals of arteries are usually inaudible; veins are audible
• Stage 3: Irreversible 
  • Limb has major tissue loss or permanent nerve damage inevitable
  • Profound sensory loss, numbness
  • Profound weakness, paralysis 
  • Doppler signals of arteries and veins are inaudible

EPIDEMOLOGY

The major cause of acute limb ischaemia is arterial embolism (80%), while arterial thrombosis is responsible for 20% of cases. In rare instances, arterial aneurysm of the popliteal artery has been found to create a blood clot or embolism resulting in ischaemia.

ETIOLOGY

Causes of acute limb ischemia include: 

• Blockage in a blood vessel (embolism) by such as by a blood clot, a fat globule, a bubble of air or other gas, or foreign material
• Blood clot (thrombosis)
• Peripheral artery disease due to atherosclerosis
• Tear in the lining of an aortic or peripheral artery (dissection)
• Major trauma
• Conditions that cause vasospasm 
  • Raynaud phenomenon
  • Shock (e.g., meningococcal sepsis, cardiogenic shock)
  • Administration of vasoactive drugs

Most acute limb ischemia is caused by embolism, thrombosis, peripheral artery disease due to atherosclerosis, or major trauma.

SYMPTOMS

Acute limb ischaemia can occur in patients through all age groups. People who smoke tobacco cigarettes and have diabetes mellitus are at a higher risk of developing acute limb ischaemia.Most cases involve people with atherosclerosis problems.

Symptoms of acute limb ischaemia include:

• Pain
• Pallor (pale appearance of the limb)
• Paresthesias (abnormal sensations in the limb)
• Pulselessness
• Paralysis

DIAGNOSIS

Acute limb ischemia diagnosed with a patient history and physical examination. The blockages associated with limb ischemia are located using one or more of the following methods:

• Auscultation
• Ankle-brachial index (ABI)
• Doppler ultrasound 
• Computerized tomography (CT) angiography
• Magnetic resonance angiography (MR angiography)
• Invasive Angiogram

ALI is diagnosed on the basis of medical history, visual examination, palpation, and Doppler examination of the peripheral arterial pulse using vascular ultrasonography and contrast-enhanced computed tomography (CT) as imaging tests

Investigation –

Suspected cases should be initially investigated with beside Doppler ultrasound scan (both limbs), followed by considering a CT angiography.

If the limb is considered to be recoverable, a CT arteriogram can provide more information regarding the anatomical location of the occlusion and can help decide the operative approach

• In order to treat acute limb ischaemia there are a series of things that can be done to determine where the occlusion is located, the severity, and what the cause was.
• To find out where the occlusion is located one of the things that can be done is simply a pulse examination to see where the heart rate can be detected and where it stops being sensed. Also, there is a lower body temperature below the occlusion as well as paleness.
• A Doppler evaluation is used to show the extent and severity of the ischaemia by showing flow in smaller arteries.
• Other diagnostical tools are duplex ultrasonography, computed tomography angiography (CTA), and magnetic resonance angiography (MRA).
• The CTA and MRA are used most often because the duplex ultrasonography although non-invasive is not precise in planning revascularization. CTA uses radiation and may not pick up on vessels for revascularization that are distal to the occlusion, but it is much quicker than MRA.^[1] In treating acute limb ischaemia time is everything.
• In the worst cases, acute limb ischaemia progresses to critical limb ischaemia, and results in death or limb loss.
•  Early detection and steps towards fixing the problem with limb-sparing techniques can salvage the limb.
• Compartment syndrome can occur because of acute limb ischaemia because of the biotoxins that accumulate distal to the occlusion resulting in edema.

Immediate treatment is needed for limb ischemia to re-establish blood flow to the affected area and to preserve the limb.

TREATMENT

Treatments for acute limb ischemia include: 

• Intravenous (IV) injection of unfractionated heparin (15–20 units/kg)

Upon the diagnosis of ALI, as long as heparin therapy is not contraindicated,an intravenous injection of unfractionated heparin (50–100 units/kg) is immediately administered to prevent the proximal and distal progression of secondary thrombosis to the site of occlusion, and a systemic administration of thrombolytic agents is not recommended. 

• Surgical treatment 
  • Thromboembolectomy
  • Bypass surgery
• Endovascular treatment 
  • Catheter-directed thrombolysis (CDT)
  • Percutaneous thrombus aspiration
  • Stent placement

extensive ischemia due to high occlusion and when time has passed since its onset, there is a high risk of severe ischemia–reperfusion injury; thus, limb amputation might be necessary to prioritize the patient’s life.

• Hybrid treatment that combines both therapies

Hybrid interventions in vascular surgery are defined as the utilization of both open surgical and endovascular techniques simultaneously in a single setting operation.

Red flags

missing stage 2 presentation

Pit falls –

window period causing peripheral limb loss

Pearls –

prompt mangement in stage -1 will save patient limb

• Daibetic control
• Frequent monitoring of limb