REB 10. Effects of Acute and Chronic Hyperglycaemia Flashcards
What are the recommended target blood glucose ranges?
refer so slide 3
What is pre-diabetes?
Pre-Diabetes: intermediate hyperglycaemia
- impaired fasting glucose
- impaired glucose tolerance
What is the blood glucose level in the FASTING state of those with PRE-DIABETES?
6.1 to 6.9 mmol/L
What is the blood glucose level in the 2-HOURS AFTER MEAL state of those with PRE-DIABETES?
7.8 to 11.0 mmol/L
What is the blood glucose level in the FASTING state of those with DIABETES?
greater than or equal to 7.0 mmol/L
What is the blood glucose level in the 2-HOURS AFTER MEAL state of those with DIABETES?
greater or equal to 11.1 mmol/L
What are the blood glucose levels of those with acute hyperglycaemia and the symptomatic levels (when symptoms arise)?
blood glucose is greater than or equal to: 8 to 15 mmol/L
symptomatic blood glucose level: greater than or equal to: 15 to 20 mmol/L (270 - 360 mg/dL)
What is the glycosuria threshold? What is the value in acute hyperglycaemia?
Glycosuria threshold is the amount of glucose the renal tubules can hold before it starts excreting glucose into the urine
the threshold is around 8 to 10 mmol/L
What are some causes of acute hyperglycaemia?
[1] Type 1 Diabetes Mellitus (decreased insulin levels)
[2] Type 2 Diabetes Mellitus (decreased insulin sensitivity of target cells)
[3] Stress Hyperglycaemia (gluceoneogenesis due to stress hormones frequently encountered during hospitalization)
[4] Other Endocrine Disorders
What are the symptoms of acute hyperglycaemia?
[1] Glycosuria (increased secretion of glucose in urine)
[2] Osmotic Diuresis (glucose in kidney tubules leads to excess water leaving in urine)
- Polyuria (excess urine)
- Polydipsia (increased thirst)
- excess loss of electrolytes (Na+, K+)
[3] Polyphagia (increased appetite)
[4] Metabolism of Proteins + Fats
- weight loss + protein deficiency
[5] Episodes leave Increased HbA1c as Diagnostic Trace
- integrated index of diabetic control
- build up of glycated haemoglobin - reflects average level of glucose to which the cell has been exposed during its life-cycle
How can insulin deficiency lead to increased ventilation? (hint: there are multiple steps)
[1] insulin deficiency leads to decreased triglyceride synthesis + increased lipolysis
[2] increase in blood fatty acids
[3] increased liver use of fatty acids leads to release of excessive ketone bodies into the blood
[4] ketosis - body burns fat for energy and liver produces ketones
[5] metabolic acidosis (e.g. diabetic acidosis when ketone bodies build up in body)
[6] increased ventilation
Acute Hyperglycaemia may be due to acute illness. True of False?
True.
Review slide 10!
Diabetic Ketoacidosis occurs as a result of the transition from [1] to [2] metabolism.
[1] glucose
[2] lipid
What is the main mechanism behind why Diabetic Ketoacidosis occurs? What are some things that may arise out of it?
- severe deficiency in insulin signalling as a result of decreased insulin secretion (no insulin to allow glucose into tissues)
- elevated levels of counterregulatory hormones (glucagon, cathecholamines, cortisol, growth hormone)
- reduced triglyceride synthesis + enhance lipolysis
- reduced protein synthesis + enhanced proteolysis
- elevated plasma free fatty acid (FFA) and amino acid levels and uptake into liver
What are some of the counterregulatory hormones that are elevated in diabetic ketoacidosis?
[1] glucagon
[2] catecholamines
[3] cortisol
[4] growth hormone
In diabetic ketoacidosis, what happens in regards to glucose production, ketosis and acidosis?
GLUCOSE:
- hyperglycaemia
- increased gluconeogensis in liver and impaired glucose utilization in peripheral tissues
KETOSIS:
- increased ketogenesis (increased production of ketone bodies, acetoacetate, beta-hydroxybutyrate, acetone acid)
- hyperketonaemia causes metabolic acidosis
What is the overall metabolic state in those with Diabetic Ketoacidosis?
[1] increased serum (blood level) GLUCOSE
[2] increased serum AMINO ACIDS
[3] increased serum FREE FATTY ACIDS (FFA)
[4] increased serum KETONES
[5] resultant METABOLIC ACIDOSIS
Explain the effects of osmotic diuresis in diabetic ketoacidosis.
- urinary excretion is in response to hyperglycaemia which causes additional loss of Na+ and K+
- leads to dehydration and electrolyte loss
- K+ lost in large quantities
- if patients have a total body deficit the development of HYPOKALAEMIA is possible (total body potassium depletion)
What is hypokalaemia? What is it a result of?
it is when there is a total body potassium depletion
it can occur during diabetic ketoacidosis as there is excessive urination and loss of both Na+ and K+ in the urine
Where does ketogenesis occur?
liver
What is ketogenesis? What occurs during ketogenesis? What are the 2 main pathways/items that are created?
Ketogenesis: increased fat metabolism
- enhanced lipolysis (adipose tissue)
- release of Free Fatty Acids (FFA) from adipose tissue
- enhanced plasma Free Fatty Acids (FFA)
- enhanced uptake into liver
- beta oxidation in liver – excess acetyl coA converted to Ketone Bodies:
- – Acetoacetate
- – Beta-hydroxybutyrate
- – Acetone (produced from spontaneous decarboxylation of acetoacetate and is slowly eliminated by respiration and excreted in urine)
What are the 3 examples of ketone bodies?
[1] Acetoacetate
[2] Beta-Hydroxybutyrate
[3] Acetone
How is acetone, a ketone body, created and gotten rid of in the body?
produced from spontaneous decarboxylation of acetoacetate
is slowly eliminated by respiration and excreted in urine)
What is Ketonaemia and Ketonuraia? What is the difference between the two?
Ketonanaemia: presence of an abnormally high concentration of ketone bodies in blood
Ketonuraia: excretion of abnormally large amounts of ketone bodies in the urine
What are some reasons that diabetic ketoacidosis (DKA) may occur?
[1] initiated by conditions that increase insulin requirements (infection, trauma, stress…)
[2] undiagnosed diabetes or failure of prescribed insulin administration at peak needs (insulin non-compliance)
Is Diabetic Ketoacidosis (DKA) a life-threatening condition? Why or why not?
Yes, it is.
- requires immediate treatment
- patients can rapidly undergo shock, coma and death
What are some symptoms of DKA?
- dehydration (polyuria, very dry mouth)
- breath that smells fruity (acetone)
- Kussmaul Respiration (deep and laboured breathing to compensate for metabolic acidosis)
- nausea and vomiting
- abdominal pain (may be severe, esp. in children)
- mental status changes (lethargy, somnolence, stupor, coma)
What can help to make a DKA diagnosis? (general - just name)
DKA Biochemical Triad
What is the DKA biochemical triad?
DKA Biochemical Triad: to help with DKA diagnosis
[1] Hyperglycaemia (>/= to 11mM)
[2] Ketonaemia (>/= 3mM)
- e.g. precision Xtra meter OR
- signficant ketonuria e.g. Ketostix
[3] Acidaemia (metabolic acidosis)
- ABG of pH < 7.3 with an anion gap of > 12 mmol/L give or take 2
What is an anion gap?
Definition: difference between primary measured cation and primary measured anions in serum
- indicator of increased concentrations of unmeasured acid anions
- continous production of ketone bodies depletes alkali reserve – Ketoacidosis
formula: Na+ - (Cl- + HCO3-)
How do you calculate the anion gap?
Na+ - (Cl- + HCO3-)
What are the 3 main treatments for DKA? (general)
[1] IV Fluid Replacement
[2] IV Insulin
[3] Potassium Replacement
What is IV Fluid Replacement and how does it work for those with DKA?
- 9% NaCl (can be up to 6 to 9L fluid deficit)
- volume expansion and fluid replacement
- correction of hyperglycaemia, ketosis, acidosis
- correct electrolyte imbalance
What is IV Insulin and how does it work for those with DKA?
- correction of hyperglycaemia, ketosis, acidosis
- reduction in ketone/increase bicarbonae blood levels
- blood glucose requires monitoring
What is Potassium Replacement and how does it work for those with DKA?
- even if plasma K+ is normal or raised, there is TOTAL BODY POTASSIUM DEPLETION
- insulin administration and correction of hyperosmolality moves potassium to the intracellular compartments, risk of hypokalemia
What are the microvascular complications of chronic hyperglycaemia?
[1] Diabetic Nephropathy (kidney damage)
[2] Diabetic Retinopathy (eye complications)
[3] Diabetic Neuropathy (nerve damage)
What are the macrovascular complications of chronic hyperglycaemia?
[1] Heart Disease
[2] Stroke
[3] Peripheral Vascular Disease
What is the difference between microvascular and macrovascular complications?
Microvascular: due to damage to small blood vessels
Macrovascular: due to damage to larger blood vessels
How are Advanced Glycation End Products (AGEs) formed?
in prolonged hypergylcaemia, protein glycation reactions lead to AGEs which are thought to be the major causes of different diabetic complications
What is the process of glycation?
[1] non-enzymatic binding of glucose with amino group of proteins
[2] complicated molecular process involving simple and complex multistep reactions
[3] prolonged high glucose levels induces glycation of various structural and functional proteins causing molecular rearrangements that lead to the formation and accumulation of AGEs
