Endocrinology Flashcards
Type 1 Diabetes patholgy
Autoimmune destruction of islet B cells by Th17 cells infiltrating, regulating inflammation.
Young children present with 90% B cell loss, adults 80-90%
How is carbohydrate and lipid metabolism regulated
Insulin and counter regulatory hormones:
Glucagon, GH, cathecholamines, cortisol
What does insulin stimulate and inhibit (LEARN)
Stimulates: -Glucose uptake in fat and muscle -Glycolysis -Glycogen synthesis -protein synthesis -K+/PO43- uptake -Fat storgae Inhibits: -Preoteolysis -Gluconeogenesis -Lipolysis -Ketogenesis
How does blood sugar change throughout the day?
Is dynamic, always changing, whe blood sugar increases insulin will follow,similar time frame, not -ve feedback
Insulin receptor binding initially causes?
Causes translocation of GLUT4 transporter to cell surface to facilitate glucose entry into cell.
Ketone production
- Ketones are made by ____ oxidation.
- Requires two steps, _____ deficiency, and ____ excess (glucagon).
- Insulin deficiency will firstly allow _____ ____ _____ in _____ tissue (activating _____) to break down triglycerides to ____ (NEFA) and glycerol which go to the ____
- In the ____, NEFA’s are _____, and then undergo ____ oxidation in the ______ by ____ ____, to form ketone bodies
- ____ excess increases liver ____ and lowers ____ Coa, activating _____ _______
- Ketones are made by FFA oxidation.
- Requires two steps, insulin deficiency, and CH excess (glucagon).
- Insulin deficiency will firstly allow hormone sensitive lipase in adipose tissue (activating lipolysis) to break down triglycerides to FFA (NEFA) and glycerol which go to the liver
- In the liver, NEFA’s are esterified, and then undergo keto oxidation in the mitochondria by acetyl Coa, to form ketone bodies
- Glucagon excess increases liver carnitine and lowers malonyl Coa, activating carnitine acetyltransferase
Ketone function
Increase when fasting, and used as energy for muscle and liver in a normal physiological sense when insulin is low. Brain food in long term. Becomes a problem when insulin is deficient, or lacking
Net result of insulin deficiency (think of what it inhbits)
- Uncontrolled proteolysis
- Uncontrolled gluconeogenesis
- Increased lipolysis (ketone production)
- Glycogenolysis, increasing glucose
- Inactive GLUT4, hyperglycaemia
Progression of keto oxidation in mitochondria is
Acetyl Coa- acetoacetyl Co- b-hydroxy-b-methylglutaryl CoA- Acetoacetate, B-hydroxybutyrate (first two are acids) and acetone
Importance of equilibrium between acetoacetate and B-hydroxybutyrate
As in the formation of BHB, NAD combines with H+. Thus in acidosis, drives production of BHB
Mechanism of DKA
A relative lack of insulin and excess CR hormones, such as glucagon due to STRESS
Anion gap in DKA
Increase in ketone bodies, acetoacetate and BHB fully dissociate, and are buffered by bicarbonate. This lowers bicarb, and decrease pH.
Anion gap will be increased due to lower bicarb, way of distinguishing cause of a metabolic acidosis.
-Bicarb is replaced by BHB and AA
Gunn thinks in DKA, what is their bicarb
Sodium and chloride balance in DKA
acute vs chronic
- In serum, anion wise there is less bicarb now, and there is ketone salt and Cl-
- Ketone anion fuses with Na+, and is lost in urine, some in blood.
Acute: Sodium and ketone loss, no change of Cl-
Chronic: NaCl replacement causes hyperchloraemia, but resolves
How are ketones detected, and what is the problem with this?
- Ketone strips to tets urine, nitroprusside reaction to measure acetoacetate
- Does not BHB, usually okay due to equilibrium.
- Problem when acidotic, due to reaction driven to BHB, lowers acetoacetate, underestimating ketonaemia
Best way to measure ketoacidosis
Serum BHB
Now use bedside tool for BHB , still underestimates but screen for ketonaemia.
To know severity, send for labs
