2: Biochemical Testing of Metabolic Decompensation

what is metabolic decompensation?

what factors lead to it?

breakdown of prev functional metabolic pathways

fatigue, stress, sickness, old age

note: a compensated syst can still function despite stressors/defects

what serious hyperglycymeic emergencies can people w diabetes get?

diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HSS)

decompensated diabetes =

presence of DKA and/or HHS

compare DKA and HHS

• body cant make enough insulin to break down glucose into E → ketogenesis → acid (ketone body) buildup in blood → DKA

• more common in young people

• symptoms: fast/deep breathing, fruity breath, tired, nausea, vomit

  
  

• prolonged hyperglycemia → severe dehydration → confusion → HHS

• insulin cant control blood glucose → excrete gluc into urine → inc urination → dehydration

• more freq in adults, elderly

• symptoms: confusion, drowsy, extreme thirst, freq urine, fever, blurred vision

both DKA and HHS are characterized by?

• hyperglycemia

• absolute (T1D) or relative (T2D) insulinpenia = [low insulin in bloodstream]

DKA and HHS differ by?

severity of dehydration, ketosis, metab acidosis

ketosis =

metab state that indicates elevated levels of ketone bodies in blood/urine

most common facotrs in DKA/HHS development

• inadequate insulin therapy (omitted or insufficient regimen)

• infection

Inadequate insulin therapy can result in?

absolute (as in T1D patients) or relative insulin deficiency (as in T2D patients undergoing stress or illness)

pathogenesis of DKA and HHS

The initial laboratory evaluation of patients with suspected DKA or HHS may involve?

• blood gas determination

• urine testing for ketones (associated with

  ketoacidosis)

• plasma testing for

  a variety of factors

patients exhibiting DKA will present with …, while those exhibiting HHS …; the differentiating factor is the …

the first clue to metabolic acidosis is a ...

explain

• metabolic acidosis, will not, presence of ketone bodies in DKA

• decreased serum bicarbonate concentration ([HCO3-])

• serum [HCO3-] < reference interval (22-30 mmol/L) → metabolic acidosis

• cause can be differentiated by serum electrolytes and arterial blood gases → define if acidemia (low blood pH) + anion gap is present

how to measure serum [HCO3-]

note: even though carbonic anhydrases are present in blood, assay uses PURIFIED ENZYMES added as reagents in assay

The amount of HCO3- present in a plasma or serum sample is typically determined by ...

The test is often referred to as … because the first step in the testing method is to …

and then, the amount of HCO3- is measured how?

• the measurement of total CO2

• "total CO2"; alkalinize a sample to convert all forms of CO2 to HCO3-

• indirectly by enzymatic methods → conversion of oxaloacetate to malate and NADH to NAD+ → use spectrometry to detect NADH consumption → use absorbance values to estimate sample [HCO3-]

how CO2 was measured historically

manometric method using a natelson microgasometer; labour-intensive; measure mixed gases from plasma in closed acid system; pressure of leftover gases after gas co2 is converted w alkali to co3

the anion gap (AG) is a useful parameter to decipher ...

The principle of … orders that anions must …

Most frequently requested biochemical profile, urea, and electrolytes?

Other cations and anions present? But need to make sure that?

• metabolic acidosis

• plasma neutrality; balance cations to maintain a neutral charge

• cation: Na+; anions: Cl-, HCO3-

• K+ and albumin; if i want to use them for anion gap calc, i need to measure them in patient AND be mindful of a different reference interval when these additional charged species in the blood are taken into account

anion gap calculation

when does AG occur?

what if the anion gap is too large or small?

AG = [Na+] - ([CI-] + [HCO3-])

[Na+] (e.g., 142 mmol/L) > combined [Cl-] and [HCO3-] (e.g., 130 mmol/L) by 12 mmol/L or greater

→ could be a sign of disorder in the lungs, kidneys, or other organ systems

causes of AG metabolic acidosis

it is ferq a result of?

• CAT MUD PILES

• anaerobic metabolism + lactic acid accumulation

what is a hallmark of absolute insulin deficiency

DKA

effects of absolute insulin deficiency (DKA) on:

1. glucose

2. fatty acids

3. ketone bodies

1. absolute insulin deficiency → glucose not properly released + metabolized thru TCA/Krebs/Citric Acid cycle → can’t gen E for body to use

2. triggers FFA gen from triglycerides in adipocytes → beta oxidize FA → form acetyl CoA → enter TCA → gen E w/out glucose

3. absolute insulin deficiency and fatty acid breakdown → so much acetyl CoA being prod + trying to enter TCA cycle → enzyme systems become overwhelmed → excess acetyl CoA converted to ketone bodies in liver

how to determine amount of ketoacidosis occuring

measure levels of ketone bodies in circulation

another tool to understand cause of AG metabolic acidosis → …; this assists in the … and …

measurement of plasma ketone bodies, diagnosis of ketoacidosis, differentiating DKA from HHS

The principal ketone bodies are … and ...

… can be metabolized to either …, through a … reaction, or …, through a … reaction.

In DKA, an … results from …

• beta-hydroxybutyrate

  (BHB); acetoacetate (AcAc)

• AcAc, acetone, non-reversible, BHB, reversible

• increased BHB: AcAc ratio, enhanced fatty

  acid beta oxidation

first test available to test ketone body presence

availability? convenience?

what exactly do they measure? BUT?

limitations?

• nitroprusside test tablets (Acetest)

• broadly, convenient → easy to perform, long shelf life

• blood and/or urine acetone + acetoacetic acid levels; DO NOT MEASURE BHB LEVELS

• Nitroprusside test tablets react mainly with AcAc in samples, with limited reaction with acetone → prod colour change

• DKA primarily produces BHB → underestimate keotsis severity when BHB:AcAc ratio is high (as in DKA) → so AcAc value may yield false negatives in DKA patient

BHB test is used to measure … to eval potential …

abnormal BHB levels =

elevated levels may require?

2 diff methods to admin BHB test:

• whole blood, serum, or plasma, presence of DKA
  
  

  
  

• GREAT THAN 0.5 mmol/L

• DKA treatment depending on patient clinical signs

• bedside ketone meters

  • used to initially diagnose DKA

  • ex. of POCT

  • ketone meters measure serum BHB levels by using a reagent strip

• lab testing

  • serum/capillary BHB testing → follow treatment response in DKA patients or used in suspected DKA or alcoholic ketoacidosis (AKA) cases

metformin

first-line medication for T2D treatment

• Urine test (urinalysis) for ketone bodies detects only acetoacetate

• Relative amounts of acetoacetate to beta hydroxybutyrate can vary based on redox state of fluid

• In diabetic ketoacidosis, beta-hydroxybutyrate predominates

• Only trace amounts of acetoacetate may be present in urine

• Urinalysis may be negative for ketone bodies in diabetic ketoacidosis → patient has DKA w large amount of ketone bodies in form of BHB

• BHB levels > 0.5 mmol/L are abnormal

• Elevated BHB may require DKA treatment

• Increased BHB:AcAc ratios in DKA due to enhanced FA beta oxidation

• Important to monitor ketone bodies, even if someone seems to suffer from pooly managed T2D