DIALYSIS MENTOR-DPSI-SEP-6-2011 BODY FLUID AND ELECTROLYTE PHYSIOLOGY BY P.DAVID BALU(P.BALAKRISHNAN DR.T.THIAGARAJAN G.PADMA PRABAKAR RAVISHANKAR DIALYSIS PERSONNEL SOCIETY OF INDIA

BODY FLUID AND ELECTROLYTE

PHYSIOLOGY:

The total body water constitutes 60% of the body weight. Some of 40% TBW is intracellular and 20% is extra cellular.

The extra cellular water constitute interstitial (16%) and plasma (4%) water which bathes the cell and surround the blood vessels and further the five litters of extra cellular water which is inaccessible because it is contained in dense connective tissue , cartilage and bone.

An infant may have as much as 80% of weight as water, a thin male have as much as 65% of weight as water, a thin female may obtain 55% of weight as water. An average male may obtain 60% of weight as water an average female obtain 50% of weight as water.

An average man weight 70kgs. The total body water is 60% of his body weight or 42ltrs. ICF 40% = 28LTRS, ECF 20% = 14LTRS. ECF= PLASMA 4% + INTERSTITIAL 16%.

It can be seen that the ICF is about twice the volume of plasma and interstitial water that portion of the ECF which is freely available for exchange. The ECF and ICF are not confined in the rigid compartments but are exchanged continuously.

The plasma which of course, circulates throughout the body and can therefore act as a bulk transporter of water and solutes in the ECF. It can also serve as a route for the even a rapid distribution of very small quantities of substances such as hormones and drugs. It is separated from the interstitial fluid by the walls of the capillaries.

Plasma Interstitil Intracell

Circulation within the plasma compartment is unidirectional with the heart serving as the pump and the kidney as a sensor and regulator of its volume. The link between heart and kidney is precise and intimate. Mechanical factors flow and pressure, neurological factors and hormonal factors provide this linkage. The I.C.F is a closed spare which indicates that there are limits to its ability to expand and that only way into and out of I.C.F is via the E.C.F.

E.C.F

KIDNEY

The body cells are specially adapted to have a major role in regulating volume and composition of the E.C.F. These include cells of organs such as the Kidney, The lung, the heart and the endocrine glands. Expansion or contraction of these spaces can be recognized by such changes as the pressure of absence of edema. Water will move equally in either direction across the cell war since the random movement of water modules will be the same in each direction. In man, therefore, the intracellular and extra cellular fluids are of comparable osmolasys and normally this is about 285 mos/kg. But suppose that the osmolality of the E.C.F should become 300. There is now an osmatic gradient, and water moves predominantly from the cells into the E.C.F until there is equalization of the osmotic pressure. Thus osmotic factors exert control over the distribution of volume between compartments. In normal circumstances, osmotic factors tend to move fluid from the interstitial space into the plasma volume, and hydrostatic pressure tends to move it in the opposite direction. The plasma and interstitial fluid of the extra cellular compartment have very similar composition except that the plasma contains a lot of protein and the interstitial fluid very little.

 

 

I.C.F

Because of their large molecular size protein cannot normally escape from the into the interstitial fluid. The osmotic pressure exerted by plasma protein in the vascular compartment is important in preventing water from leaking into the interstitial compartment. If this colloid osmotic pressure is severely reduced due to depletion of plasma proteins. Example in nephritic syndrome water will leak into the interstitial space and become evident as edema. If two solutions of different concentrations are separated by semi permeable membrane, the concentrations will tend to equalilize because water rapidly passes through the membrane from the area of lower concentration to the higher concentration. At a slower rate, solute diffuses through the membrane from the area of higher concentration to lower concentration. REGULATION OF BODY WATER

• 1. Intact thirst mechanism 2.Appropriate renal handling of water and solutes.

• Intact ADH release and response.

• Serum tonicity is maintained within a range of 285 mosm\kg H2o due to regulation of water balance. Derangements are largely reflected by changes in the serum sodium concentration.

• Sodium and its ions are the main determinants of plasma osmolality, thus 2times serum sodium will approximate the serum osmolality.

• The incorporation of BUN and glucose is important when these concentrations are increased.

• Under normal circumstances we all maintain a water balance so that intake and our losses are equal.

• Sources of loss include moistening the expired air, sweating and urine. Because of losses from sites other than kidney, our urine output is always less than our total intake.

• When we are deprived of water, the urine becomes smaller in volumes and more concentrated.

• When our fluid intake is high, the weather is cool and our unmeasured losses are small, our urine output will increase.

• The ability to vary the volume and concentration of the urine in accordance with our needs to lose or retain water is a precise role of the kidney function.

• When we have a plentiful supply of water, the urine may be much more diluting that plasma, when water is in short supply it can be as much as four times as concentrated as plasma.

• Normally about 99% of GFR will be reabsorbed by tubules as a passive osmotic event, and the active movement of sodium and chloride out of the lumen.

• The filtered urine remained isotonic which plasma up to the end of the proximal tubule, what ever the final urine concentration.

• The urine was always hypotonic at the end of loop of henle, what ever the final concentration.

• The wall of entire ascending limb allows solutes to move out the lumen but does not allow water to follow the osmotic gradient.

• The thick ascending limb is the site of a transport system which utilizes sodium, potassium, chloride.

• The thin ascending limb doesn’t have an active transport system; it is relatively permeable to sodium chloride. The osmotic environment that develops outside the tubules favors diffusion of sodium chloride out of the ascending limb.

• Isotonic fluid moves slowly through the loop of henle, solute is removed from the tubule and added to the interstitial, leaving water behind. The interstitial fluid is relatively more concentrated than the urine in the ascending limb. Thus by the end of the loop of henle the urine has become hypotonic.

• The descending limb of the loop of henle is freely permeable to water it will share all the concentration steps of the interstitium around it. Water moves passively across its wall to equalize osmolalities.

• The hair pin configuration of the loop is essential inorder to trap and maintain concentration gradient.

• Under conditions where water conseavation is not needed, the urine remains dilute until it leaves the kidney because the collecting duct is effectively water proof. Thus the urine is affected by the osmotic gradient through which it passes.

• When, however, water conservation is required ADH released from the hypothalamus, renders the wall of the collecting duct permeable to water. As a result, the osmotic effects of the interstium cause the removal of water from the collecting duct, thus concentrating final urine.

HYPONATREMIA

Hyponatremia is a SNa below 135 meq/l. This is the most frequent electrolyte abnormality in hospitalized patients. Hyponatremia is caused by i) excess water intake with normal renal function or ii] a continued solute-free water intake with a decreased renal capacity for solute- free water excretion. Hyponatremic disorders require measurement as sosm and assessment of ECV.

Volume physical findings laboratory dindings

Hypovolemic skin – poor skin turgor Increased HCT, S.Protien

` Skin – No edema BUN and creatinine

ABD – Normal UNa < 20 meq/l

Resp – clear

CVS – JVP Flat

- No S3

RR – Normal

BP – postural drop BP > 15 mmHg

- Normal or low resting BP - GC patient looks wan tired

EVOLEMIC Normal examination Normal

HYPERVOLEMIC BP – normal or High Decreased HCT,

HR – Resting Tachycardia S. protein, BUN/CR

RR – Tachypnea

Resp – Cackles, wheezing, pleural effusion

CVS – JVP elevated

ABD – positive hepatojugular reflux

EXT – sacral, Facial or pedal edema

EVOLEMIC HYPONATREMIA

Evolemic hyponatremia in patients without hypovolemia or edema, although TBW is increased by apporxinatedy 3-5 ltres.This disorder is due to 1) an excessive secretion of ADH, 2) potentiaed effect of ADH 3) an inappropriate action of ADH is the important cause for this type. The urine is inappropriately concentrated for the degree of hyponatremia and hyposmolity.The Urinary Na is usually >20 mq/l. Failure to excrete a water load can establish the diagnosis of syndrome IADH but may produce danger hyponatremia. SIADH secretion generally produced with malignancies, pulmonary disorders, and CNS disorders.

THE DIAGNOSIS OF SIADH REQUIRES.

• Hyponatemia with serum hypo-osmolality • Urine osomolality that is greater than serum osmolality • urine Na > 2meq/l • Normal renal, thyroid, adrenal function • Patient not on diuretics

• The Evolemic hyporatremia can usually treated by restriction of water intake to ltr/day

• SNa should be corrected with the rate of 1.5 to 2.0 meq/l/hr • Monitor BP ,electrolytes, neurological status and renal function • Initiation- of salt and water diuresis- frusemid 1mg/kg may required • Maintain a urine output of approximately ltr/hr • Measure urinary Na and K losses hourly and replace with N.S • Required sodium concentration can be calculated by -required Na mmol

= SNa (Desired) – SNa [observed] x TBW TBW = 0.6 x wt in kg

Example: For 70/kg man has a SNa of 120 meq/L

Required Na = 135 – 120 = 15x42 ltr = 630mmol

Since lL of NS contains 154 mmol of Na, you will require 4L of NS to increase s.NA to135mml/l, OR the volume of excess water needed to be calculated by

Actual Na meq/l x current TBW – Normal TBW

Normal

120

135 x 42 = 37.5 L. water excess = current TBW – normal

42L – 37.5 = 4.5L

Carry out your morphologist order strictly. Dialysis personnel should not prescribe any medicine without nephrologists order.

HYPOVOLEMIC HYPONATREMIA: - Body volume + S. Na decreased. Initial therapy should include discontinuation of diuretics, correction of G.I losses and expansion of ECV with 0.9/Nacl

Example: 70 kg person who now weigh 64 kg has SNa of 120meq.The total body water is 60% x 70 kg = 42liters

A 6 kg wt loss decrease TBW to 37 liters

Normal Body Na = 42ltrs with 140mg = 5880 meq

Current Body Na = 37 litter with 120mg = 4440meq

Na deficit = 5880meg – 4440 = 1440meq

One third of Na deficit can be given as 0.9 Nacl over 6hr and the reminder over 48hr. potassium deficit need to be corrected if vomiting, diarrhea or volume depleted factors

HYPERVOLEMIC HYPONATREMIA: - Body Volume increased, S.Na decreased

• Restrict salt and water • Reduce diuretics as prescribed

HYPERNATREMIA:

• S.Na more than – 145 meq/L causes • Inadequate intake of water • Hypothalamic dysfunction • Diabetes Insipidus • G.S losses • Mannitol administration

TREATMENT

• Check SNa ,SOsm • Correct volume and water deficit as ordered by nephrologist • In patients who are volume depleted, hyponatremia can be corrected by

giving I v. NS until the patient is hemodynamically stable and then change to ½ NS or D5W to correct remaining water deficit.

• In patients who are not volume depleted ½ NS or D5W can be used to correct the water deficit.

• Water Deficit = S.Na (ob) – S.Na [normal] x 0.6 • Hypernatremia with fluid 0verload can be treated with administration of

lasix 40mg I.V as ordered by nephrologist

ASSEMENT AND MANNGEMENT OF VOLUME STATUS

The assessment of volume status is an integral part of physical examination. There are only three basic status of volume status that a patient can have volume depleted, normovolemic and volume overload.

• Observe the patients fluid status patients who are volume depleted look tired, wan and drawn. Patient who are volume over load look uncomfortable, anxious and restless

• Measure the heart rate and BP, first with the patient supine and then after the patient stands for 1 minute. If the patient is hypertensive in the supine position, standing BP is not necessary

• An increase in heart rate >15 beats/mt, a fall in systolic or diastolic BP indicate postural hypotension and which may indicate intravascular volume depletion

• A resting Tachycardia with low stroke volume may be seen with volume depletion

• The volume overloaded patient must also generate a tachycardia in a effort to increase forward flow and thereby relieve the lungs of pulmonary congestion

• Tachypnea and crackles may be seen in the volume over load patient with pulmonary edema.

• Examination of IJ veins is one of the most helpful components of the volume status. Once the internal jugular vein pulsation is identified, measure the perpendicular distance from the sternal angle to the tope of the Column of blood. A volume overloaded patient will usually have an elevated JVP greater than 3cm above the sternal angle.

• ABD – An enlarged liver and a positive hepatojugular reflux may be manifestations of the volume overload state.

• Skin- Thorax and sacral or pedal edema indicates interstitial fluid excess.

• Cr/urea Ratio - A ratio of less than 12 is indicate volume depletion • Maintain I/o chart properly •

SELECTION OF CORRECT I.V.FLUID

• Water is important in the body because it serves as a solvent for a variety of solutes. Solutes can be either electrolytes or non electrolytes

• Non electrolyte solutes that have no electrical charges such as glucose and urea.

• Intravascular volume is mostly made up of water, which act as a solvent to dissolve and transport electrolyte and non electrolyte.

• Glucose distributes widely thorough both intracellular and extra cellular spaces where as sodium is limited primarily to the extra cellular space. Albumin remains largely with in the IC space.

• D5W consists of 50g of dextrose dissolved in 1L of water. It has an osmolality of 252mosml/l, which will prevent the patient’s RBCS from shrinking or swelling. Dextrose can be expected to equilibrate rapidly among the intravascular, interstitial and intracellular spaces, and water will follow along quickly by osmosis.

• NS has osmolality of 308 mosm/L and although slightly hypertonic, is not cause cell shrinkage. NS will stay predominantly in the extra cellular space somewhat longer than a glucose infusion because sodium does not readily move intracellular.

• Albumin and plasma will stay in the intravascular space for many hours, since albumin is large molecule that doesn’t easily traverse the endothelial pores of the blood vessels. The half-life of albumin within the intravascular space is 17-20 hrs.

• In patents with intravascular volume depletion may treated with I.V NS or D5W also useful.

• In patients with extra vascular volume excess, D5W infusion is best choice, NS or albumin infusion will worsen volume status.

• 2/3 and 1/3 Ringer lactate may be beneficial for poor oral intake patients.

• Get nephrologists order before infusion of I.V fluids and administration of any drugs.

ELECTROLYTE DISORDERS POTASSIUM PHYSIOLOGY POTASSIUM:- Potassium is important for healthy nervous system and regular heart rhythm. It helps to prevent stroke, aids in proper muscle contraction and work with sodium to control body’s water balance. Potassium is important for chemical reaction s with in cells and aids in maintaining stable BP and in transmitting electro chemical impulses. 98% of body k is in the intracellular fluid. In muscle, the ICF (K) is close to 150mm and this is 30-40 times higher than the K in the ECF 4mm. This K gradient is the result of K transport in to the cells by the NAKATPase and of K Diffusion out of the cell passively, down the K gradient. These events generate resting membrane potential. During hypokalemia or hyperkalemia, the change in ECF K is proportionally larger than that in the ICF. A rise in the ECF K can depolarize cells and lead to arrhythmias. During hypokalemia cells tent to hyperpolarize and this can also lead to cardiac arrhythmia.

The daily potassium load is 50-150 meq. Approximately 90% of the K ingested is normally eliminated in the urine, with small potion excreted in the stool and sweat. However, when renal function is decreased, the GI tract can eliminate up to 30% of the intake, K secretion by the colon and sweat glands is stimulate by aldosterone. The serum potassium concentration is a general indicator of body K. However, because only about 2% of total body K is in the ECF and 98%

is in the ICF, small loses or gains by cells can cause large changes in the serum K+.

ACID- BASE STATUS AND K+ SHIFTS ACROSS THE CELL MEMBRANE

• In acute metabolic acidosis, K may leave the ICF for charge balance, and during acute metabolic alkalosis K enters the ICF.

• Only metabolic acidosis caused by NAHCo3 loss leads to initial hyper potassium owing ICF buffering .A normal kidney and aldosterone response returns the plasma K to normal.

• In contrast, a gain of an organic acid does not cause High potassium, insulin lack or hypoxia may lead to a K+ shift into the ECF and to hyperkalemia.

• Potassium does not shift with acute respiratory disorders. INSULIN Insulin causes K+ to shift into cells. Several mechanisms may be involved. For example insulin causes an increase in the resting membranes potential; possibly owing to an increase in the NAKATPase activity, and this attract K+ into the ICF. Alternatively insulin can cause synthesis of phosphate enters in the ICF and these anions attract K+ into cells. Quantatively, if the basal insulin concentration halves the ECF K+ rises by about 0.5 mm within 30min. Administration of insulin should cause a significant fall in the ECF K+ this is especially important during treatment for hyperkalemia.

CATECHOLAMINES: - catecholamine plays an important role in determining the distribution or k+ across the cell membrane.

• B1 – adrenergic stimulate rennin release from the kidney there by increasing aldosterone production and K+ excretion.

• Catecholamine promote glycogenolysis, which leads to hyperglycemia and insulin release, insulin causes k to move into the ICF

• D- Adrenergic action inhibits insulin release from pancreatic B cells, this tends to promote hyperkalemia direct d- action lead to a k * shift out of cells during hypokalemia.

ALDOSTERONE: aldosterone stimulates cellular K’ up take and facilities renal k excretion. It stimulates the Na-k pump, not only in the kidney but in other organs as well, a deficiency frequently cause hyperkalemia.

PHYSIOLOGY OF POTASSIUM EXCRETION: - almost all the filtered k’ are reabsorbed prior to the distal nephron in normal kidney. The k excreted in the urine is mainly due to k secretion in the late distal convoluted tubule and colleting duct.

• Water is reabsorbed in medullary collecting duct; this elevates the urine k+.

• Reabsorption or secretion of potassium occurs in medularly collecting duct and seems to be important for the urine k+ during hypokalemia or hyperkalemia.

Aldosterone lowers the member potential across the luminal membrane, and this favors cation secretion in to the lumen. The higher Na+ in the cell increases flux through the basolateral NaKAT pase, which brings K+ from the ECF into principal cells. The net effect is K+ movement from the ECF to the lumen.

• Potassium excretion = urine K+ x UV • Adrenal insufficiency impairs K+ excretion and causes sodium wasting.

ACTH administration causes hypocalcaemia. • K+ secretion requires that Na+ be reabsorbed; the Na+ reabsorbed into

the ICF of the cortical distal nephron is pumped out into the ECF via the NaK AT pase.

• Na reabsorption and the naKATpase are both stimulate by aldosterone. • The K+ in principal cells rises and K+ move passively into she luminal

fluid. • In the presence of aldosterone, the luminal K+ is close to 10 X that in

the ECF. • Since aldosterone only elevates the luminal K+, factors that increase the

urine flow rate also augment K secretion

HYPOKALEMIA: Hypokalemia is termed when S.K+ decreases 3.Omeq\l.

ETIOLOGIY:

Urine K+ > 20 mmol/ day: renal losses

• Diuretics, osmotic diuretics • Renal Tubular Acidosis • Hyperaldosteronism • Glucocorticoid excess • Magnesium deficiency • Chronic metabolic alkalosis • Vomiting, NG suction,

EXTRA RENAL LOSSES

• Diarrhea • Intestinal fistula.

SHIFT FROM ECF TO ICF

• Acute Alkalosis • Insulin therapy • Vitamin B12 therapy • Salbutamol

MANIFESTATIONS:

Cardiac: PAC, PVC, Digoxin toxicity,

ECG-T wave flattening, U waves, St- Segment depression.

NEUROMUSCULAR:- weakness, depressed deep tendon reflexes, paresthesis,

MISCELLANEOUS: - diabetic incipidus, metabolic alkalosis.

ASSESSMENT:

Assess the severity; the severity of the situation should be determined according of the serum potassium concentration, the ECG findings, and the clinical setting in which hypokalemia is occurring.

If severe: serum K+ < 3.0 < with PVCs

• Notify your nephrologists • place the patient on continuous ECG monitoring • IV replacement therapy ay be required i.e. 10mmol/Kcl in 100 ml D5W

given IV over 1 hour. • KCl in small volumes should be given through central IV. Lines, since

these high concentrations of potassium are Sclerosing to pherepral veins. Further replacement can be achieved with maintenance therapy containing up to 40to60 mmol kcl/l of IV fluid at a maximum rate of 20 mmol/l. Monitor s.k intermittently.

• Potassium can also be given by administration of the liquid salt by NG tube or supplementation.

• Consult and carry out Nephrologists order properly

HYPER KALEMIA: - S.K>6.0 mmol/L

CAUSES.

• Excessive intake • Blood transfusion • Potassium sparing diuretics spironolacton, amiloride, triamterene • Hypoaldosterone •

SHIFT FORM ICF TO ECF

• Acedemia • Insulin deficiency • Hemolysis, burns, tumor lysis. • Drugs- Digoxine, arginine, beta-blocker. • Leukocytocysis • Thrombocytosis

MANIFESTATIONS

CARDIAC:

• Fatal ventricular dys arrhythmias • Peaked T waves • Depressed ST segments • Prolonged PR interval • Small or absent p waves • Wide QRS complexes • Ventricular fibrillation cardiac arrest •

NEUROMUSCULAR

• Weakness, often beginning in the lower extremities • Paresthesias • Depressed tendon reflexes

LAB INVESTIGATIONS

• Serum electrolytes • Serum creatinine, BUN, Cr – clearance. • Arterial blood gasses • WBC, platelet count, HCT • ECG, • Renal ultra sound, Bladder catheterization

MANAGEMENT:

• Continuous ECG monitoring is required if the potassium level is above 6.5 mmol/L

• If serum. K+> 6.5mmol;lNotify your nephrologists • Correct acidemia or hypovolemia • Give kayexalte 30 gm with 100 ml of 20% sorbitol orally • Promote K+- Shift into cells with 500 ML 10% glucose containing three

amples of NaHCo3 ( lamp=4.6 mmol/l) and 20 units of rgular insulin at 75 ml/hr until more definitive measures are taken

• Give calcium glulconate 10 ml of a 10% solution • Give 50% DW with 10 units of regular insulin will help to shift potassium

form EC to the ICF. • Give kayexalate enema- 50 gm kayexalate powder with 200 ml of sorbitol

or 20% DW per Rectum. • Perform Heamodialysis • Perform – PD if hemodinamically unstable • Monitor the serum K+ concentration every 2 hrs until it is below 6.6

mmol/l . • Consult and carry out Nephrologists orders.

CALCLUM AND PHOSPHORUS:

CALCIUM:

Calcium is vital for the formation of strong bones and teeth and for the maintained for healthy gums. It is also important in the maintenance of a regular heart beat and the transmission of nerve impulses. Calcium is needed for muscular growth and contraction and for the prevention of muscle cramps. Calcium lowers blood cholesterol level and helps prevent cardiovascular disease. It is needed for blood clotting and prevents cancer. It may lower BP and prevent bone loss associated with osteoporosis as well. Calcium provides energy and participates in the protein structuring of RNA and DNA. It is also involved in the activation of several enzymes, including lipase, which breaks down fats for utilization by the body. In addition. Calcium maintains proper cell membrane permeability, aids in neuro muscular activity, helps to keep the skin healthy and protect against the development of pre eclampsia during pregnancy.

MEASUREMENT OF CALCIUM IN BLOOD.

Total serum calcium concentration normally is 8-8 to 10-4meq/l it consists of three portions 1. Protein bound calcium – 40%, 2.ComplexeD calcium 15%, which is bound to several anions citrate, lactate, sulfate, phosphate, and 3. Ionized calcium 45% which is the biologically active component. Ionized calcium can be measured anaerobic ally on freshly drawn serum with lon exchange electrodes and ranges from 4.0 to 4.8 g.

FACTORS ALTERING TOTAL SERUM CONCENTRATION:

S. Albumin- decrease of 1gm/ dl in serum albumin decreases total serum calcium by 0.8 mg. dl.

Tourniquet; change of plasma water into tissues elevates the total S.CA

PH: The binding of calcium to protein increases PH. A change of 0.1 PH units causes a change of 0.12 mgldl of ionized calcium in the opposite direction

PTH: PTH increases lionized calcium at the expense of protein bound calcium. All patients with hyperparathyroidism have elevated ionized calcium.

S. Phosphate: HIGH PO4 will lowers ionized calcium, then lowers total s. calcium..

CALCIUM AND PHOSPHATE IMBALANCES IN RENAL FAILURE.

• The decreased GFR in renal failure causes retention of phosphate and an increased plasma phosphate

• The ionized plasma calcium level decreases to compensate the excess plasma phosphate

• The diseased kidneys are unable to metabolize vitamin D to its active metabolic, 1, 2.5 DHCC thus the hypocalcaemia worsens.

• The parathyroid glands respond to the low plasma ionized calcium and secrete parathoromone PTH.

• Osteoclasis is stimulated by the PTH and cause resorption of calcium and phosphate from bones to plasma.

• Both plasma calcium and phosphate level rise concomitantly and the normal calcium phosphate is not maintained.

• Acidosis of renal failure aggravates the bone demineralization. • Excess aluminum may be deposited in the bones and increase bone

problem. • When the calcium phosphate product exceeds approximate 70 mg,

calcium phosphate crystals form and precipitate in brains, eyes, gums, valves of the heart, blood vessels, soft tissue and other part of the body.

HYPERCALCFMIA: - total S.ca >11.0 mg

Causes and pathogenesis of hyper calcemia:

INCREASED VITAMIN D INTAKE:

This condition is seen most commonly in dialysis patients. This 1,25 D3 stimulates GI absorption of calcium and augments renal tubular reabsorption of calcium

• Tuberculosis: TB produce elevation of 1, 25 D3 levels from activated monocytes. This 1.25 D3 cause hypercalcemia

• Primary hyperthyroidism: Primary hyperthyroidism or increase PTH stimulates 1.25 D3 and increased GI and renal absorption of calcium cause hyper calcemia

MALIGNANCY:

Breasts, lung cancer and multiple myloma may destruction of local bone, collect osteoclasts by tumor and may produce ectopic PTH may cause to increases S.Calcium

MILK ALKALI SYNDROME: This condition is caused by ingestion of large amounts of calcium and alkali. The alkalosis increases protein binding of calcium and stimulates tubular reabsorption thus preventing renal excretion of calcium cause hypercalcemia.

THIAZIDE DIURETICS:

Thiazide diuretics increase Ca+ reabsorption in the proximal and distal tubule. Thiazide can worsen hyper calcemia in patients with primary hyper thyroidism

PHYSICAL FINDINGS

HEENT - corneal calcification

CVS -Short QT interval, prolonged PR interval, dysrhythmia hypertension,

GI Anorexia, nausea, vomiting, constipation.

Abdominal pain, peptic ulcer disease

Neuro - Insomnia, restlessness, delirium, dementia, psychosis, coma

MSS - Muscle weakness, bone pain, hyporeflexia, fractures.

MANAGEMENT

• If serum Ca+ >11.0 mg/ dl notify your Nephrologists. • If severe hypercalcemia s.ca>13mg. treat immediately

• Start letter of N.S I.V over 1 hr if hypotonic states • Give furosemide 40-80 gm Iv every 3hr if hypervolemic status • Monitor urine output, urine Na, K, Mg every 4 hr. • If diuresis is to be continued over 24 hrs, replace Mg losses with 1 gm

mg so4 added to I.V fluids • Discontinue VIT-D, thiazide and theophyline if presence. • Encouraged exercise • Consult and carry out Nephrologists orders. • Hem dialysis may require.

HYPOCALCAEMIA: Total S.Ca+ < 8.5 mg\l with normal albumin.

CAUSES:

• Hypoalbuminea • Hypomegnesemia • Respiratory alkalosis • VIT- D deficiency • Hypo Thyroidism • Hyper phosphatemia

PHYSICAL FINDINGS:

HEENT - papilledema

CVS - prolonged QT- interval without U-waves.

GI - Abdominal Cramps

NEURO - Depression, irritability, confusion tetany, seizures

MANAGEMENT:

• Notify nephrologists • Check S.Ca, P04, S. Albumin • If hypoalbuminia present Add 0.2 mm/l for every 1gm/dl of hypo

albumin • If hyper phosphatemia present- give 1 amp D50 with 10 Units of regular

insulin as per Dr’s prescription • If severe hypocalcaemia give 30-40ml of CA.gluconate in 500 ml of 5%

D over 4 to 6 hrs

• Monitor serum Ca+ • Start Ca+ and vit D supplements as per Dr advice • Monitor ECG for digoxin patients • During Ca+ infusion avoid bicarbonate solution • Consult and carry out Nephrologists orders.

PHOSPHORUS

Phosphorus is needed for bone and teeth formation, cell growth, contraction of heart muscle, and kidney function. It also assists the body in the utilization of vitamins and conversion of food to energy. A proper balance of calcium, phosphorus and magnesium should be maintained at all times. If one of these mineral is present either excessive or insufficient amount it will have adverse effect on the body.

HYPER PHOSPHATEMIA: S. P04 LEVEL EXCEED 6 MG\DL

CAUSES:

• Decreased GFR < 20 ml/mint • Increased Tubular reabsorption- hypothyroidism • Cytotoxic therapy- Tumorlysis phosphorus into ECF • Excessive intake of vit –D3 • Excessive dietary phosphate intake

MANAGEMENT

• Notify Nephrologists • Advice to reduce the intake of p04 foods • Give phosphate binders • Encouraging to do regular exercise • Stop vit-d, Avoid alcohol • Provide Adequate dialysis • Consult and carryout Nephrologists orders.

HYPOPHASPHATEMIA: _ S. Po4 level < 2.5mgdl

CAUSES:

• Prolonged malnutrition • Chronic diarrhea • Vitamin D deficiency • Hyperparathyroidism • Glycosuria • ECF- expansion

MANAGEMENT

• Notify Nephrologists • Advice to increase the intake of Po4 foods of high protein • Prescribe VIT.D • Recommend to drink skimmed milk, Milk products • Stop phosphate binders • Perform exercise and Avoid alcohol • Consult and carryout Nephrologists orders

MAGNESIUM: - Magnesium is a vital catalyst in enzyme activity and energy production. It assists in calcium and potassium uptake. Magnesium is necessary to prevent the calcification of soft tissue. Magnesium combined with pyridoxine may prevent calcium oxalate and caP04 kidney stone. Magnesium may help prevent cardiovascular disease, osteoporosis, certain forms of cancer and it may reduce cholesterol levels. Magnesium can help prevent depression muscle weakness and twitching and aids no maintaining the body’s proper pH balance.

PATHO PHYSIOLOGY:

With a normal daily intake of 300 mg of magnesium per day, 30- 40% absorbed. The thick ascending limp of the loop of henle is for the bulk of Mg reabsorbed

HYPOMAGNESAEMIA. S.MG ABOVE 2. 4MGLD.

CAUSES:

• Chronic renal failure, ARF,Mg so4 administration SIGNS AND SYMPTOMS:

• Reduced tendon reflexes • Confusion, lethargy • Hypotension, and cardiac depression

TREATMENT

• Notify nephrologists • Give calcium I.V as per dr advice • Stop mg containing antacids • Provide adequate dialysis • Consult and carryout Dr’s order

HYPOMAGNESAEMIA:- S.mg< 1.8 mg\dl

CAUSES:

• Chronic alcoholism • Diabetic ketoacidosis • Hypercalcemia • Loop diuretics • Poor dietary intake or magnesium • Digitalis toxicity

MANAGEMENT

• Notify nephrologists • Administer I.V Mg SO4 as per Dr advice • Advice to take high mg food, such as dairy products, fish meat, apples,

apricot banana, garlic, grapes , green leafy veg, lemon and wheat, avid hyperkalemia.

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ACID BASE DISORDERS

ACID BASE – PHYSIOLOGY

H+ and PH; The Hco3 and PCo2 together determinant the ECF. H+ and their relationships are shown as H+ = 23.9xPCo2 (HCo3 ). The H+ is depicted in terms of respiratory component Pco2 and a renal component HCO3. The normal value are ( H+ ) 40nm, Pco2 40 mmHg, and HCO3= 24 mmol/l. The H+ is often reported as its negative log, the pH. The pH transformation does not improve the understanding of acid base physiology.

Bicarbonate ( Hoc3): The ECF HCo3 is an important determined of the acid base status and is referred to as the metabolic compound of the bicarbonate buffer system. The HC03 can be determined in two ways. Either calculated from the H+ and Pc02 or inferred from the total Co2 determination, which is the part of electrolytes when HCo3 loss occurs whatever reason, the H+ increases, owing to displacement of the Hco3 buffer equilibrium to the left.

H+ Hco3 H2 Co3 H20 + Co2 in addition the Pco2 can be viewed as a near constant owing to its very large turnover rate. Pco2; The PCo2 is the partial pressure of Co2 in arterial blood and is the respiratory component of the bicarbonate buffer system. Co2 is continuously produced by metabolism ( 10mmol/mt) and equal quantity is removed by the lungs. Thus, in hypoventilation the pco2 rises rapidly, where as t falls rapidly during hyperventilation. There are two processes that lead to an Acidemia (reduced HCo3 or increased Pco2). and two that lead to an alkalemia (increased Hco3 or decreased Pco2.) Thus there are 4 primary disturbances of acid- base balance.

ACIDS AND BASES: An acid is a compound that is capable of proton ( H+) donation, where as a Base is any compound that is capable of proton acceptance. An acid ( HA) dissociates. Yielding the H+ and its conjugate base. While chemists divide acids into strong and weak ones on the basis a of their dissociation constant = HA=H+A

BUFFERS: A buffers minimizes The change in ( H+) when either a strong acid or a strong base is added. It is most selective in defending the H+ against acids or bases , when it is 50% dissociated .

THE ECF HCO3 BUFFER SYSTEM: The HCO3 buffer system is the major ECF buffer and the assessment at it is components provides the basis for the clinical evaluation of the ECF HCO3 and the PCO2 as is a is evident from the HCO3 buffer system equilibrium.

H+ HCO3 ca H2 CO3 H2o+ CO2

The H+, HCO3 and PCo2 are reflect and acid base status of ECF.

THE ICF BUFFERS: sixty percent of an acid load is buffered in the ECF. The major ICF buffer is imidazole ring in histidine.HCo3 is also an important ICF buffer in metabolic acidosis. Daily H+ load; an individuals is net daily acid load is approximately 1MML/KG/D, which comes from the liver, largely owing to enables of the protein constituents of the diet.

REGULATION OF ACID BASE BALANCE: the metabolic processes of the body can only function within narrow limits of alkalinity and acidity. Blood PH, which reflects the H+ concentration in plasma water, is 7.4 in normal circumstances. A pH below 7.0 or above 7.7 is not compatible with life for very long. There is a generally accepted normal range from 7.35—7.45. If the pH falls below 7.35 indicates an acidosis, above 7.45 indicates an alkalosis. Maintenance of a steady ph depends on three interconnecting system includes buffers, the lungs and the kidneys. A buffer is a substance which takes up an acid or alkali without significant change in Ph.If an acid is added to the body. E.g. during diabetic ketoacidosis, the pH of the body is held relatively constant by buffers. The buffers in the intracellular water are predominantly proteins. The major buffers system in the ECF is HCO3. HCO3 combines with H+ to form carbonic acid H2 Co3, which dissassociates to CO2 and H20

HCO3 + H H2 CO3 CO2 + H2O. The Intracellular and extra cellular buffers act simultaneously to defend the pH against sudden changes in H+ concentration .A fall in Ph stimulates respiratory centre in the brain to increase the ventilation rate. Increased ventilation results in more CO2 being blown of from the lungs. This respiratory compensation for acidosis is limited by the mechanics of ventilation. It should be noted that alkalosis results in a decreased ventilatory rate, a subsequent retention of Co2 and H+ production.

An excess acid or alkali load is excreted by the kidneys. In the normal course of events our diet, when broken down in the body, contained more acid than alkali and the main route of excretion of acid is through the kidney. Renal acid excretion is a slow process, the rate of acid eliminate being increased or decreased according to the needs of body. H+ ions are excreted into the distal tubules and disposed in three main ways.

1. By the combination of HCO3 to produce CO2 and water, co2 diffusion back into the blood stream.

2. By excretion wish buffers specially phosphates, which take up H ion 3. By combination with ammonia and excreted is an ammonium salt

NH3+H+ = NH4. In patients with CRF there are not enough serving nephrons be excrete all the acid adequate and a mild metabolic acidosis may develop. Renal damage due to tubular damage such as pyelonephritis, tend to be accompanied by more severe acidosis than glomerulonephritis.

RESPIRATORY CAUSES OF ACID BASE DISTURBANCE:-

The major role of the lungs from the acid base point of view is to maintain the PCO2 constant by removing the 10 mmol of Co2 produced/mt by normal metabolism. Failure to remove the C02 leads to the generation of H+ and Acidemia, where as excessive CO2 removal results in Alkalemia.

Chronic lung disease with Co2 retention can lower the blood PH by increasing carbonic acid. The features will be raised PCo2 on blood gas analysis and raised plasma bicarbonate. The patient will also have clinically obvious lung disease. The condition is called respiratory acidosis.

METABOLIC ACIDOSIS

Metabolic acidosis represents a primary decrease in plasma bicarbonate concentration and decreases blood pH. causes:- The metabolic acidemia are conveniently divided into normal anion gap and high anion gap varieties. The normal anion gap Na+K-Cl+HCO3= 10-12 mmol .Remember that for every decline in S. Albumin of 10gm/l, add 4 to the calculated anion gap. Failure to correct for hypoalbumi nemia may lead to high anion gap serious acidemias

NORMAL ANION GAP ACADEMIA

I. Loss of HCo3

a. Diarrhea b. High output ileostomy c. Renal tubular acidosis d. Carbonic anhydrate inhibitors

High Anion Gap Acidemia

a. lactic acidemia b. Ketoacidosis c. Renal failure d. High flux dialysis with acetate buffer e. Drugs aspirin, ethylene glycol, methyle alcohol.

CLINICAL PRESENTATION.

- Nausea, vomiting, and abdominal pain. Respiratory - Compensation produces rapid deep respiration - Severe acidosis can be associated with decreased

myocardial contractility, hypotension, pulmonary edema and true hypoxia

- The ABG low pH, Low HCO3, PCO2 TREATMENT:

- Calculate the amount of HCO3 required as HCO3 HCO3 deficit wt x 0.4 x ( desired ---measured HCo3)

- Notify Nephrologists - Administer I.V Na HCO3 as per Dr. advice - Give o2 inhalation as per Dr. Advice - Monitor Vital signs carefully - Stop ketoacid production by administering 5-10

units of insulin stat and 2 -6 units /hr for continuous infusion as per Dr. advice

- Monitor K+ and sugar. - Correct anemia with blood transfusion - Avoid rapid infusion of NAHCo3, prevent ventricular

dysarrythmias - Give dialysis as per Dr Advice. - Consult and carry out nephrologists order

RESPIRATORY ACIDOSIS

- - PH< 7.35 - PCo2 high - HCO3 normal or high

CAUSES:

ACUTE AIRWAY OBSTRUCTION

- Pleural effusion ‘Pneumo thorax - Severe lung disease

- Hypokalemia, Hypophosphatemia - Neuropathies.

CLINICAL PRESENTATION:

- Bradypnea - Drowsiness - Confusion - Papilledema- swelling on the optic nerve.

TREATMENT:

- Perform ABG

- Give O2 inhalation as per Dr. Advice - Give IV NaHCO3 as per Dr. Advice - Consult and carry out dr`s orders

METABOLIC ALKALOSIS.

Metabolic Alkalosis is due to a primary increase in plasma HCO3 and increase in blood PH. This HCO3 excess can result from ECF hydrogen loss.

PH; 7.45.PCO2, normal or low .HCO3 low, - vomiting. GI loess

- Diuretic therapy, - Hypokalemia

- Certain GI diseases and diuretics can induce the loss of fluid containing cl in a greater concentration than bicarbonate leading to ECF volume contraction and rise in HCO3 concentration.

CLINICAL PRESENTATION:

Hypoxia, Musle cramps, weakness

Volume contraction BUN and CR HIGH

TREATMENT:

Notify nephrologists Monitor ABG electrolytes, RFT Monitor vital signs Give O2 inhalation as per dr advice Give I.V N.S as per Dr advice Give KCL infusion as per Dr. advice Consult nephrologists

RESPIRATORY ALKALOSIS:

PH > 7.45,PCO2 decrease,HCO3 decrease

CAUSES:

Pulmonary disease CHF Pneumonia Pulmonary embolism Anemia, hyper thyroidism Fever

CLINICAL PRESENTATION

Hypo apnea Muscle cramps Seizures, confusion Cardiac arrhythmias.

TREATMENT

Notify Dr. Monitor vital signs Consult and carryout Drs order

REFERENCES 1. HAND BOOK OF NEPHROLOGY 2. HAND BOOK OF DIALYSIS 3. RENAL NURSING