Metabolic, Volume and Ion Disturbances. Salty Pickle with a Hint of Sugar

Metabolic, volume and ion disturbances. Salty pickle with a hint of sugar.

KANIZSAI PÉTER - BERÉNYI TAMÁS

BUFFERS METABOLIC ACIDOSIS

pH < 7,35 CO2 HCO3 < 22 +/+ +/- O2/sat ANION GAP (6-12 mEq/L)

nature.com A decreased anion gap (< 6 mEq/L) may suggest the following:[4]

 Hypoalbuminemia  Plasma cell dyscrasia  Monoclonal protein  Bromide intoxication  Normal variant

A normal anion gap (6-12 mEq/L) may indicate the following:[4]

 Loss of bicarbonate (ie, diarrhea)  Recovery from diabetic ketoacidosis  Ileostomy fluid loss  Carbonic anhydrase inhibitors (acetazolamide, dorzolamide, topiramate)  Renal tubular acidosis  Arginine and lysine in parenteral nutrition  Normal variant An elevated anion gap (>12 mEq/L; “mud pilers”) may indicate the following:

 Milk-alkali syndrome  Uremia  Diabetic ketoacidosis  Propylene glycol  Isoniazid intoxication  Lactic acidosis  Ethanol ethylene glycol  Rhabdomyolysis/renal failure  Salicylates  HIPERNATRAEMIA  HIPEROZMOLARITY  VOLUME OVERLOAD (FREE WATER!)  WIPLASH ALKALOSIS  HIPOKALAEMIA  DECREASED OXYGEN DOWNLOAD (LEFT SHIFT)  INCREASED LACTATE PRODUCTION  INTRACELLULAR ACIDOSIS  CSF ACIDOSIS  HYPERCAPNIA METABOLIC ACIDOSIS

INCREASED ANDOGENOUS HYDROGEN ION PRODUCTION EXOGENOUS ACID LOAD

HYDROGEN ION ORIGINATING FROM INCREASED PROTEIN INTAKE AND EXCEEDING EXCRETORY LIMITS

RENAL BICARBONATE LOSS

RENALLY COMPENSATED RESPIRATORY ALKALOSIS METABOLIC ACIDOSIS

DECREASED MYOCRDIAL CONTRACTILITY DECREASED SVR (ARTERIOLAR DILATATION/VENOUS CONSTRICTION) INCREASED INOS SYNTHESIS CENTRALIZED BLOOD VOLUME – IMPAIRED SPLANCHNIC CIRCULATION PULMONARY VASOCONSTRICTION HYPERVENTILATION (FATIGUE) INCREASED METABOLIC RATE (DECREASING ATP AND 2-3 BPG LEVELS) HYPERGLYCAEMIA AND HYPERKALAEMIA AMS (CONFUSION) SIRS CELL MEMBRANE ION PUMP DEFICIENCY METABOLIC ACIDOSIS + H /NORMAL PCO2

RENAL FAILURE? DIABETES MELLITUS?

POISONONG? (SALICYLATE; ALCOHOLS; PARACETAMOL) MEASURE CHLORINE - CALCULATE! ANION GAP HIGH NORM / LOW

MEASURE LACTATE! HYPERCHLORAEMIA

HIGH NORM / LOW ↑K+ NORM/ K+

PERFUSION DEFECT, ALCOHOLIC EARLY AKI RENAL TUBULAR ACIDOSIS PIOSONING* KETOACCIDOSIS HIPOALDOSTERONISM TUBULAR DAMAGE CONGENITAL CAUSE RHABDOMYOLYSIS ACID INPUT DIARRHOEA HYPERALIMENTATION CURED DKA Hyperkalaemia

High potasium levels

„PSEUDO”  CONTROL

DECREASED EXCRETION INCREASED INTAKE  AKI ICF SHIFT TO ECF  DIRET POTASSIUM  ACIDOSIS  TUBULAR DISEASES  BLOOD  SEVERE CATABOLISM  OLIGURIA  RHABDOMYOLYSIS  HYPOALDOSTERONISM  K-SPARING DIUR.  MEDS (K-SPARING  CELL/TISSUE DAMAGE DIURETICS; CYCLOSPORIN; ACEI; NSAID)  MINERALOCORTICOID DISTURBANCE  DRUGS: (ALDOSTERON ANTAG.; DIGITALIS INTOX.; SCOLINE, ßBLOCKER….)  HYPEROSMOLARITY BICARBONATE (5-10 MIN) INSULIN+SUGAR RRT (30MIN) (MINUTES) …. FRUSEMIDE

INTRACELLULAR POTASSIUM SERUM POTASSIUM↑ CALCIUM ENTRY (MUSCLE) (BLOOD) (HEART MUSCLE)

CALCIUM GLUCONATE (1-5 PERC)

Hypokalaemia HYPERCHLORAEMIA

 ARTEFICIAL (SMALL ANION GAP)  METABOLIC / ENDOCRINE  HYPERNATRAEMIA  DIABETES INSIPIDUS OR DIABETIC COMA  HYPERPARATHYROID STATES  METABOLIC ACIDOSIS se. Cl > 106 mEq/L  RENAL TUBULAR ACIDOSIS  GASTROINTESTINAL  VOMITING pH <7.35  PROLONGED DIARRHOEA CO2< 22 mEq/L.  KIDNEY DISEASE  LOSS OF PANCREATIC JUICE (FISTULA)  MIDBRAIN INJURY (NEUROGENIC HYPERVENTILATION)  DRUGS  ANDROGENES  OESTROGENES  STEROIDS  DIURETICS (CARBONIC ANHYDRASE - INHIBITOR) HYPOCHLORAEMIA METABOLIC ALKALOSIS DIARRHOEA  DEHYDRATION SYNDROMES (VOMITING) VOMITING NG TUBE  LOW CHLORINE LEVELS HYPONATREMIA  MUSCLE SPASTICITY SUPRARENAL CORTICAL INSUFF.(ADDISON)  TETANY RENAL FAILURE  SUPERFICIAL BREATHING OEDEMA – COMGESTIVE HEART FAILURE  HYPONATREMIA PSEUDOHYPONATREMIA  WEAKNESS SALT LOOSING NEPHRITIS  MUSCLE TWITCH INFUSION THERAPY SWEATING  SEWATING BURNS  FEVER DIETARY PROBLEMS DRUGS se. Cl < 98 mEq/L LOOP DIURETICS ALDOSTERONE pH >7.45 ACTH CORTICOSTEROIDS CO2> 32 mEq/L BICARBONATE se.osmol < 280 mOsmol/L LAXATIVES GENETIC DISEASES CYSTIC FIBROSIS BARTTER’S SYNDROME HYPONATRAEMIA

 NAUSEA AND VOMITING  HEADACHE  CONFUSION (AMS)  FATIGUE  WEAKNESS  RESTLESSNES, AGITATION  MUSCLE WEAKNESS, SPASMS  CONVULSIONS  OBS  COMA

seNa < 135mEq/L

Serum osmolarity

280-295mOsmol/L <280mOsmol/L >295mOsmol/L ISOTONIC HYPOTONIC HYPERTONIC

Urine osmolarity

<100mOsmol/L >100mOsmol/L „WATER RENAL INTOXICATION” seNa < 135mEq/L

HYPOVOLAEMIA NORMOVOLAEMIA HYPERVOLAEMIA

Urine Na Urine Na Urine Na

> 20 mEq/L < 10 mEq/L > 20 mEq/L < 10 mEq/L RENAL LOSS EXTRARENAL RENAL OEDEMA*

* HEART FAILURE CIRRHOSIS NEPHROSIS SY. POTASSIUM SIAD OSMOSTAT ENDOCRINE* DEPLETION * HYPOTHYREOID GLYCOCORTICOID SIAD SIAD

HYPERNATRAEMIA HYPERNATRAEMIA IS SUCH AN HYPEROSMOLAR STATE WHERE THE DECREASE OF TBW IS DISPROPORTIONATE TO THE ION CONCENTRATION – IT IS REALLY A „WATER-PROBLEM” RATHER THAN AN ION DISTURBANCE

PATHOPHYSIOLOGY OF HYPERNATRAEMIA TÜNETCSOPORTOK COGNITIVE DYSFUNCTIONS ASSOCIATED LETHARGY, OBTUNDATION, CONFUSION, WITH NERVE CELL SHRINKING CONVULSIONS, NYSTAGMUS, MYOCLONUS, IRRITABILITY THE CLNICAL PROCESS OF DEHYDRATION ORTHOSTATIC DECREASE IN BP, TACHYCARDIA, OLIGURIA, DECREASED SKIN TURGOR OTHER ASSOCIATED PROBLEMS WEIGHT LOSS, GENERAL WEAKNESS HYPERNATRAEMIA

1. HYPOTONIC FLUID LOSS (WATER AND ELECTROLYTE LOSS) 2. PURE WATER LOSS 3. USE OF HYPERTONIC SALINE

TO ESTABLISH THE DIAGNOSIS:  ELECTROLYTE LEVELS (NA+, K+, CA2+ )  BLOOD SUGAR  CN, CREATININ  URINE ELECTROLYTES (NA+, K+)  URINE AND PLASMA OSMOLARITY  24 HR COLLECTED URINE  PLASMA AVP/COPEPTIN LEVEL (IF REQUIRED) Diabetes insipidus

Central diabetes insipidus

Renal diabetes insipidus

Polydipsia-polyuria syndrome Differential Diagnosis of Diabetes insipidus

. State-of-the art diagnosis: 1. Stimulation of AVP release via a water deprivation test 2. Indirect measurement of AVP release by monitoring of urine osmolality and volume during water deprivation (ability to concentrate urine). 3. Additional desmopressin administration to differentiate nephrogenic DI from central DI.

. Direct AVP measurement therefore is not the diagnostic reference standard because of its methodological limitations (instability of analyte and uncomfortable assay handling)

CT-proAVP (hs Copeptin) Suspicion of diabetes insipidus with polyuria-polydipsia syndrome CT-proAVP basal (in the morning, fasting, after 8h dehydration)

CT-proAVP CT-proAVP >=2,6 - 20 pmol/L CT-proAVP <2,6 pmol/L >20 pmol/L

Central Diabetes Renal Diabetes insipidus totalis insipidus Ratio of CT-proAVP-Delta (8 to16h) and Serum-Na+ (16h) = CT-proAVP-Index

CT-proAVP-Index CT-proAVP-Index <20 >=20

Central partial Primary diabetes insipidus polydipsia The available data demonstrate limitations of current biochemical tests for the differential diagnosis of DI, potentially leading to incorrect diagnosis and treatment. The newly available assay for C terminus of the vasopressin precursor, holds promise for a higher diagnostic specificity and simplification of the differential diagnostic protocol in DI. Advantages for the diagnostic routine with CT-proAVP

• Significantly higher diagnostic accuracy for all variations of diabetes insipidus and primary polydipsia

• Considerably eased differential diagnosis of polyuria-polydipsia syndrome

• Reduced physical and psychological exposure of the patient due to simplified WDT and redundancy of desmopressin stimulation

• Support of safe therapeutic decisions with highly sensitive measurement values

• Overall cost reduction due to reduced complexity, less lab consulting and no prescription of desmopressin WHAT FLUID? HOW FAST ?  IN OLIGURIA, HYPOTENSION: 0,9 % NACL  HALF OD THE DEFICIT OVER 24 HRS  NORMOTENSION: D5W  THE REST OVER 24-48 HRS METABOLIC ALKALOSIS

H-ION LOSS H-ION TRANSFER TO IC VOLUME EXOGENOUS ALKALI CONTRACTION ALKALOSIS

HyPOKALAEMIA! - I.C. H-ION SHIFT → INCREASED BICARB. REABSORPTION RESPIRATORY ALKALOSIS

CENTRAL HYPOXIA INDUCED PULMONARY JATROGENIC PATHOLOGY(RESP. HYPERVENTILATION PATHOLOGY CENTRE) HYPERVENTILATION PE TRAUMA PNEUMONIA TUMOR ASTHMA STROKE PULM. OEDEMA DRUGS WEAKNESS, MYALGIA, POLYURIA, ARRHYTMIAS HIPOVENTILATION SYMPTOMS OF HYPOCALCAEMIA AFFECTED ORGANS

CNS CIRCULATION OTHER

 INCREASED  ARRHYTHMIAS  HB. DISSOC. CURVE LEFT NEUROMUSCULAR  DECREASED SHIFT ACITIVITY CONTRACTILITY  HYPOKALAEMIA  DECREASED ICP  DECREASED CEREBRAL  DECREASED PERFUSION RESPIRATORY TRIGGER RESPIRATORY ACIDOSIS

INADEQUATE ALVEOLAR CO2 OVERPRODUCTION EXOGENOUS CO2 LOAD VENTILATION MALIGNANT HIPERTERMIA INTOXICATION, CENTRAL RESPIRATORY DEPRESSION: REBREATHING DRUGS, TRAUMA, BLEEDING, OBESITY

NEUROMUSCULAR DISORDERS: GBS, MG, ORGANOPHOSPHATE, MYOPATHIES

LUNG OR CHEST WALL ABNORMALITIES: CHEST TRAUMA, PTX, HTX, COPD ACUTE EXACERB., PULM. OEDEMA, ARDS

AIRWAY OBSTRUCTION

OTHERS: INADEQUATE MECHANICAL VENTILATION CHRONIC RESPIRATORY ACIDOSIS

PH NORMAL

PCO2 ↑↑ PO2 ↓

DANGERS OF O2 THERAPY!

PINK PUFFER VS BLUE BLOATER

5% DEXTROSE (DEST.VÍZ)

SA / RINGER

kOLLOID

CAPILLARIS MEMBRAN

CELLULARIS MEMBRAN VOLUME STATE

HYPOVOLAEMIA NORMOVOLAEMIA HYPERVOLAEMIA

CAUSE AND EXTENT OF VERŐVOLUMEN

FLUID LOSS NORMÁL SZISZTOLÉS FUNKCIÓ (QUALITATIVE/QUANTITATIVE)

FLUID REPLACEMENT  CRYSTALLOID GYENGE SZISZTOLÉS FUNKCIÓ  COLLOID  BLOOD PRODUCTS

VOLUMEN ELŐTERHELÉS/VOLUMEN VOLUME STATE REASSESSED CRYSTALLOIDS

DISTRIBUTES IN THE WHOLE ECV SAME COMPOSITION AS OF THE INTERSTITIAL FLUID SAME OSMOTIC PRESSURE AS OF THE PLASMA MIGHT CAUSE TISSUE OEDEMA MIGHT CAUSE ACIDOSIS IN HIGH QUANTITY

COLLOIDS

SOLUTIONS CONTAINING MACROMULECULES REMAIN IN THE INTRAVASAL SPACE AND BIND WATER IF COLLOID OSM. PRESSURE = PLASMA OSM. PRESSURE ISOVOLAEMIC HAEMODILUTION IF COLLOID OSM. PRESSURE = PLASMA OSM. PRESSURE → HYPERVOLAEMIC HAEMODILUTION PLAZMA SA RINGER RL HALF RD BALANCE NORMAL OSMOLARITY 288 312 150 426 PH 7,4 5-7 5-7 3-6 GLUCOSE 5 5% NA 140 147 130-140 K 4,2 4,0 4,5-5,0 MG 3 0-3 PHOSPHATE 1,25 CL 103 155 96-109 LACTATE 1-1,5 0-29 ACETATE - 0-27 NA:CL 1,36 PLAZMA SA RINGER RL HALF RD BALANCE NORMAL OSMOLARITY 288 308 312 150 426 PH 7,4 4,5-7 5-7 5-7 3-6

GLUCOSE 5mmol 5% NA 140 154 147 130-140 K 4,2 4,0 4,5-5,0 MG 3 0-3 PHOSPHATE 1,25 CL 103 154 155 96-109 LACTATE 1-1,5 0-29 ACETATE - 0-27 NA:CL 1,36 1 PLAZMA SA RINGER RL HALF RD BALANCE NORMAL OSMOLARITY 288 308 312 300 150 426 PH 7,4 4,5-7 5-7 5-7 5-7 3-6

GLUCOSE 5mmol 5% NA 140 154 147 131 130-140 K 4,2 4,0 5,4 4,5-5,0 MG 3 0,5 0-3 PHOSPHATE 1,25 CL 103 154 155 112 96-109 LACTATE 1-1,5 27 0-29 ACETATE - 0-27 NA:CL 1,36 1 1,17

VOLUME OVERLOAD

ALLERGIC REACTION ACIDOSIS

pH 4,5-7

Na 154 Cl 154

STRONG ION DIFFERENCE COAGULOPATHY

J.TRAUMA – 2011.

PRIMARY DAMAGE OUTCOME SECONDARY DAMAGE

VARIABILITY THE CAPACITY OF A SHIP TO ABSORB DAMAGE AND MAINTAIN MISSION INTEGRITY

ACIDOSIS

HYPOTHERMIA

COAGULOPATHY

 URINE OUTPUT  URINE SODIUM AND OSMOLARITY  MAP (CPP AND APP)  BUN  SVI  HR  LACTATE(CLEARANCE)

 PH, BE, HCO3  SMVO2, OR SCVO2  PCO2  TISSUE PCO2 (SUBLINGUAL, GASTRIC)  EXTRAVASCULAR LUNG WATER (EVLW)  INTRA-ABDOMINAL PRESSURE (IAP)  …

26 YEAR OLD GUY WORKS ON A BUILDING SITE IN HOT WEATHER. COMPLAINS OF NAUSEA AND WEKANESS. HE IS OFFERED FLUIDS BUT REFUSES IT BECAUSE OF FEAR FROM VOMITING. IN TWO HOURS HE LOSES CONSCIOUSNESS AND AN AMBULANCE TAKES HIM TO S THE ED.

OTHERWISE HEALTHY, DRUG ALLERGY: PENICILLIN THIS IS DAY 3 ON THE BUILDING SITE, BUT GETS EXHAUSTED VERY EARLY B THE TEMP IS 37 °C IN SHADE. LOOK, LISTEN AND FEEL! POCT BLOODS A IMAGING

CTAS/HUTAS SUGGESTED THERAPY R THERAPEUTIC END POINTS DRY, WARM AND PALE SKIN. GCS: 14/15. RR:110/70, P: 134/MIN, SPO2: 94 % PH:7,51, PCO2:49 HGMM, PO2:85 HGMM, BE:5, NA:159, K:3,0, HCO3: 29, LACTATE: 1,9, SAO2: 96 % CN: 11, CREAT: 112, INR:1,09, FBC: RBC:5,8, HT:0,54, HB:168, A WCC:8,9, PLT:198

19 YEAR OLD KNOWN T1D PATIENT IS TRANSFERRED TO THE ED. SHE IS S UNCONSCIOUS.

SHE’S BEEN DIABETIC SINCE THE AGE OF 10 AND HER DIABETES IS QUITE BRITTLE. SHE IS VERY THIN, BMI:17. NKDA. ACCORDING TO HER MOTHER SHE’S BEEN HAVING A TEMP FOR DAYS, SHE HAS ACHEST COUGH, AND YELLOWISH SPUTUM. SHE ATE LESS AND THEREFORE B HALVED HER USUAL DOSE OF INSULIN. GCS:1-T-4, NO NEURO DEFICIT. RR:80/50 HGMM, P:125/MIN, SPO2: 78 % (FIO2:0,21) PH:6,97, PCO2:17, PO2:61, BE:-19, NA: 132, K:5,7, HCO3:14, LACTATE: 2,8, SAO2:78 % OTHER BLOODS: BUN: 17, CREAT:132, INR:1,25, FBC: RBC:4,2, HT:0,48, A HB: 148, WCC:22.000, PLT: 98, PCT:3,8

CTAS/HUTAS OTHER INVESTIGATIONS SUGGESTED THERAPY R THERAPEUTIC ENDPOINTS BLOOD SUGAR > 11MMOL/L

BICARBONATE (HCO3) < 15 MMOL/L (VENOUS) PH < 7.3

 PREGNANCY  BICARB < 5 MMOL/L  PH< 7.1  HYPOKALAEMIA (<3.5 MMOL/L)  GCS < 12  SPO2 < 92 %  ANION GAP > 16  SBP < 90 HGMM / 60> BPM < 100  UNCONTROLLED DM  HYPEROSMOLAR STATE  STRESS (HYPERGLYCAEMIAA)

HYPERGLYCAEMIA

DKA KETOSIS METABOLIC ACIDOSIS

 ALCOHOL  HYPEREMESIS  LACTATE ACIDOSIS  KETOTIC HYPERGLYCAEMIA  HYPERCHLORAEMIC ACIDOSIS  FASTING  URAEMIA  SALICYLATE (!) IV ACCESS 0.9% NACL - 1000ML/HR INSULIN + 500ML + 2G KCL/HR

POCT  ABG (PH; BICARB)  BLOOD SUGAR  ANION GAP  ELECTROLYTES (VOLUME STATE)  URINE (KETON)

START INZULIN SHORT ACTING IV (4-6U/H)

MONITORING  LEVEL OF CONSCIOUSNESS (GCS – IF REQUIRED MECH. VENT.)  CVP / VOLUME; SCVO2 ....  ECG, IABP …. PERFUSION  UOP  OXYGEN SUPPLY