water, sodium and potassium homeostasis

Transcription

1 Lectre-3 water, sodim and potassim homeostasis Dr. Khalid Al-Ani Department of Clinical Pharmacy Faclty of Pharmacy Water & sodim balance Internal and external balance Internal balance is the distribtion between different body compartment External balance match inpt and otpt Total body water (TBW) /70 kg adlt = 42 liter = 60% of body mass distribted in two compartments 2/3 (66%=28L)in the intracelllar flid compartment (ICF) 1/3 (33% = 14L)in the extracelllar flid compartment (ECF) Total body water (TBW) - distribted in two compartments. (conti) ECF 75% (11L) of ECF is interstitial flid (ISF) 25%(3L) of ECF is intravasclar (IVF) (plasma) CSF is abot 150 ml 1

2 some facts Water is passively transported in the body, freely permeable throgh cell membranes ( ICF and ECF) Sodim is the major extra celllar cation (95%) Total body sodim /70 kg adlt 4200 mmol 50% in ECF 40% in bones 10% ICF some facts some facts The capillary endothelial is freely permeable to sodim [Na + ] of the ISF is eqal to that of plasma The capillary endothelial is only slightly permeable to plasma proteins [protein] of the ISF is << that of plasma 2

3 some facts The capillary endothelial is only slightly permeable to plasma proteins some facts Diffsion = net movement of particles (soltes) down concentration gradient to establish eqilibrim between two sides of membrane Osmosis = diffsion of water from high concentration to low concentration [protein] of the ISF is << that of plasma Movement of Body Flids Water distribtion between compartments is determined by 1. Osmolalilty -controls water distribtion between ICF and ECF Osmolality Osmolality is the nmber of dissolved particles (molecles and ions) per kg of soltion affect movement of water cross cell membrane 2. Colloid osmotic pressre -controls water distribtion between IVF and ISF Low osmolality High osmolality 3

4 How can we calclate osmolality? Osm is eqal to the sm of all molecles and ions cross cell membrane/nit wt The major contribtor to ECF osmolality is Na, and other sch as glc, rea and k + Osmal gap plasma protein or lipids Osmal = 2 [Na + ]+ 2[K + ] + [glc] +[rea] = 2x135 +2X = mmol/kg Tonicity # of solte particles in soltion which can effect osmotic pressre (e.g. Na + ), which means soltes which are not freely permeable thogh cell membrane, cases movement of water into and ot of the cells Tonicity is not the same as Osmolalilty bt often sed interchangeably sbstances sch as alcohol and rea does not contribtes to tonicity since they are readily diffsible down concentration gradient and reach eqilibrim Hypertonic -- high amont of solte Hypotonic = dilte Colloid osmotic pressre exerted by plasma proteins across cell membrane 4

5 q at arterial end of capillary, CHP > COP, so flid moves ot of the capillary qat venos end of capillary, COP > CHP, so, flid moves from arond cells; containing wastes and CO2 moves into capillary Reglation of external water balance Water intake is variable, and largely depends on social habits water intake = water otpt Average daily water otpt and intake Minimm daily intake need for maintenance of water balance is 1100ml Obligatory losses Sorces -Skin 500 -diet and drnk Lngs 400 -oxidative -Gt 100 metabolism 400 -Kidneys ml 1500ml 5

6 Water intake is controlled by Sensation of thirst and otpt by anti-diretic hormone(adh) Reglation of external water balance-cont change body water change Osmolalilty ( ) Loss of water from ECF increases Osmolalilty. This will case -movement of water from ICF ECF -Stimlates hypothalams thirst center which promotes the desire of drink -Stimlates ADH secretion Reglation of external water balance-cont Reglators of Vasopressin release conseqently a small volme of concentrated rine is prodced (Max 1200mmol/kg) 1. Osmotic control hypothalamic Osmoreceptor sensitive for small changes in osmolality as small as 1% 6

7 Reglators of Vasopressin release conti. above a 282mosmo/l the concentration of ADH increases Below 282 mosmo/l ADH is ndetectable in plasma 2. baroreceptor Decreased blood volme/pressre stimlates the release of ADH baroreceptor is Less sensitive than the osmoreceptors; detect a 8 10% change in volme or pressre Factors affecting ADH secretion Stimlated by: High osmolality Low blood volme Low blood pressre via Angiotensin II and volme receptor stress inclding pain Inhibited by: Low ECF Osmolalilty Hi blood volme Hi blood pressre Alcohol Reglation of external sodim balance Na inpt = Na otpt There is an obligatory loss for Na (10mmol/day) kidneys, (skin and GIT to less extend) 7

8 Sodim distribtion (conti) There are massive internal trnover of Na GIT = 10mmole/day kidney = 25000mmol/day In disease, GIT can be a major loss of Na + Sodim and ECF volme Serm normal range = mmol/l Na is most important ion in reglating water balance [Na + ] affects ECF osmolarity [Na + ] affects blood pressre & ECF volme 1. The glomerlar filtration rate (GFR) sodim balance is maintained by reglation of its renal excretion which affected by 70% of filtered Na + is reabsorbed in the proximal tbles Less than 5% reach the distal tbles 8

9 2. The glomerlar filtration rate (GFR)-conti Redced GFR less Na + is filtered and excreted and Vice versa 2. Renin Angiotensin system (II) How RAS works? 3. Atrial natriretic peptide (ANP) -Works at kidney 9

10 Atrial natriretic peptide (ANP) ANP is a 28 AA polypeptide secreted by right atrim in response to volme expansion, which cases stretching of the myocardim Atrial natriretic peptide (ANP) conti. ANP Lowers blood volme and pressre antagonize RAS Two other strctrally similar peptide has been identified (BNP) and (CNP) Water Homeostasis Two types of disorders: Water depletion: Usally accompanied Na + depletion Is de to decreased intake or increased loss --> Hyperosmolality Water excess: Increased intake or decreased loss --> Hypoosmolality Water and Na + depletion losses are> than intake. Pre water depletion is less common (may occr in DI and from lng) Na + can't excreted with ot water 10

11 Water depletion( hypovolmia) Clinical featre Flid lost from blood vessels, leads to decreased ECF volme Signs Decr d rine otpt Weight loss (throgh flid weight) Can leads to hypovolemic shock Water depletion( hypovolmia)- conti. Symptoms of hypovolemia Thirst, dryness of the moth Decr d blood pressre Increased heart rate Cases of water depletion Decreased intake Infancy, old age, nconsciosness, dysphagia Cases of water depletion-conti Increased loss From kidney Diabetes insipids Increased osmotic load (DM) osmotic diretics From skin From lngs From gt diarrhea in infant 11

12 Water excess (hypervolemia) Which one is more dangeros, the losses of pre water of isotonic flid? Usally occr de to impaired water excretion Healthy Kidney can excrete 20ml/min Cases cerebral over-hydration Hyponatraemia is invariable present Water excess (hypervolemia) conti Clinical featre With incr d ECF volme Weight gain (flid weight) Dilted rine Increased blood pressre Can also edema Confsion and headache Cases of water excess Increased intake - Complsive water drinking -Excessive IV flids 12

13 Cases of water excess Decreased excretion - Renal failre -Inappropriate or ectopic secretion of vasopressin (SIADH) -Some drgs (e.g: cortisol) SIADH = syndrome of inappropriate ADH secretion Prevents rinary excretion of water Reslts in a state of water excess: Low plasma osmolality; low plasma Na + High rine osmolaltiy No edema normal renal and adrenal fnction Major Cases of SIADH Major Cases of SIADH-conti Tmor -ectopic prodction of ADH -carcinoma of the lng prostate & pancreas Inappropriate secretion -plmonary diseases -pnemonia -Tberclosis Pain e.g. postoperative Drgs- enhanced release of ADH or response to ADH. Cyclophosphamide, carbamazepine, Prozac, narcotics 13

14 Sodim excess Too mch Na + or too little water Can be de to increased intake or decreased excretion Characteristics of excess sodim: Increases osmolality movement of water from ICF to ECF Cells dehydrate Overall increased ECF volme (at expense of the cell volme) Cases of sodim excess Increase intake Administration of hypertonic IV soltion Renal retention decreased GFR Acte and chronic renal failre Cases of sodim excess conti. primary mineral corticoid excess Cshing syndrome Conn s syndrome Secondary mineralcorticoids excess CHF Nephrotic syndrome Sever liver disease i.e. cirrhosis 14

15 Cases of sodim excess conti. Electrolyte Imbalances Sodim excess conti. Loss of excess of water skin Lng renal Clinical featre Peripheral edema Lethargy Nerological dysfnction (dehydration of brain cells) hypertension weight gain Sodim excess and edema Cases of edema Accmlation of isotonic flid in interstitial space (increased ISF) Decreased colloid oncotic pressre -hypoproteinemia Sodim depletion Na+ can be lost from the body in either isotonic or hypotonic flids. In each case there will be a decrease in ECF volme 15

16 Sodim depletion-conti The normal responses to hypovolemia are: increases aldosterone secretion low rine volme de to decreased GFR increase ADH in case of sever hypovolemia Cases of sodim depletion Excess loss From kidney -diretic phase of acte renal failre -diretic therapy -osmotic diresis -mineralcortical deficiency- Addison disease Cases of sodim depletion-conti Sodim depletion cont From gt -vomiting -diarrhea From skin -excessive sweating, brns inadeqate intake -rare Clinical featres reslts from decreased ECF Symptoms weakness, apathy, postal dizziness sign weight loss tachycardia hypotension 16

17 Clinical and laboratory findings in sodim and water depletion Na depletion H2O depletion Plasma Na PCV N or S ECF volme N Plasma rea Urine Conc. Hypo and hypernatremia Hypo and hypernatremia define as 5mmole above are lower the healthy controls hyponatremia freqently fond in hospitalized patients de to sick cell syndrome Cases of Hyponatremia Cases of Hyponatremia-conti Water and/or Sodim Excess of water ( diltional ) SADH Sick cell syndrome CHF Water and/or Sodim Loss of Na + from GIT vomiting diarrhea (rine Na + <20mmol/l) Loss of Na + from kidney -Addison disease (rine Na+ >20mmol/l) 17

18 Hypernatremia Hypernatremia Sodim and/or Water Sodim and/or Water Hypernatremia is mch les common than hyponateremia -Loss of water > Na + GIT - diarrhea, Renal osmotic diresis, fever -Increased body Na + steroid excess Potassim balance Potassim is the major intracelllar cation 2% in the ECF gradient maintained by Na/K pmp Potassim cont d Serm K + level maintained within a narrow limit Decreased K + -increases cardiac mscle excitability arrhythmia -mscle weakness Cardiac arrest occrs in both high and low K + 18

19 External K + balance controlled by kidney and to less extent by GIT. 99% of filtered K + reabsorbed in the proximal tbles. obligatory losses is 10-20mmol/day Factors effecting K + excretion 1. amont of Na + available for absorption 2.The relative availability of H + and K + ions in the distal cell Factors effecting K + excretion 3. aldosterone directly and indirectly stimlated K + excretion Internal distribtion Factors effecting K + shifting from ICF to ECF inslin deficiency acidosis hyperosmolality cell death 19

20 Internal distribtion-conti Factors effecting K + movement into cells Hypokalemia Serm K+ < 3.5 mmol/l after inslin therapy alkalosis decreased K intake (rare) Tran-celllar K + shift -alkalosis -inslin therapy renal Hypokalemia conti. Osmotic diresis diretics thiazides decreased Cl - absorption loop diretics increase tblar flow, ths Na delivery to the distal Mineralcorticoid excess primary and secondary cabenoxolone, liqorice RTA GIT Hypokalemia conti. diarrhea vomiting (K + loss, alkalosis, RAS) 20

21 Hyperkalemia Serm K+ > 6.5 mmol/l Remember: Abot 98% K + is intracelllar leaving only 2% extracelllar. Hence, a K + shift from the ICF to the ECF of only 2% can doble the plasma [K + ]. Serm K+ > 6.5 mmol/l reqired rgent treatm. Potassim Imbalances Hyperkalemia qsprios or artifact hemolysis qtrans-celllar K + movement tisse damage systemic acidosis inslin deficiency Potassim Imbalances Hyperkalemia Hyperkalemia conti. qdecreased K+ excretion -acte renal failre - chronic renal failre ( late) -K + sparing diretics ACE inhibitors Clinical featre Mscle weakness, paralysis Change in ECG pattern qaddison s disease 21

22 22 Metabolic responses to trama