Lecture 23 - Clinical Endocrinology

Question 1

Type I Diabetes histology and time course?

Answer 1

Lymphocyte (Th17) infiltration -> destruction of insulin production; youth have >90% destruction, older have 80-90%

Question 2

Counter regulatory hormones?

Answer 2

glucagon, cortisol, adrenaline and GH

Question 3

Processes stopped by insulin?

Answer 3

gluconeogenesis, glycogenolysis, lipolysis, ketogenesis, proteolysis

Question 4

Processes promoted by insulin?

Answer 4

uptake by muscle and adipose, glycolysis, glycogen synthesis, glycogen synthesis, protein synthesis, uptake of ions (K, PO3)

Question 5

Insulin 24hr progression?

Answer 5

highest when waking, spikes during meals, lowest overnight - non stable homeostasis influenced by cortisol

Question 6

Insulin Receptor biochem?

Answer 6

insulin binds, GLUT4 receptor activated, glycogen synthesis, conversion of glucose -> pyruvate -> fatty acids

Question 7

Making ketones - fat?

Answer 7

insulin inhibits hormone sensitive lipase, which ‘mobilises’ fat by stimulating beta-oxidation (induced by glucagon),

Question 8

Making ketones - liver?

Answer 8

insluin deficiency -> increased hepatic FA oxidation -> increased plasma and liver FFA + excess glucagon -> excess ketogenesis

Question 9

Making ketones - mitochondria?

Answer 9

acetyl CoA -> acetoacetate -> B hydroxybutyrate (can go back) or acetone; increases anion gap, product ketones become acid form, causing a decrease in bicarbonate, ketone bodies circulate as anion gaps - therefore in DKA HCO3 is replaced with B-hydroxy-butyric acid and acetoacetic acid

Question 10

Na and Cl balance?

Answer 10

Na-B-hydroxybutyrate and Cl- from NaCl, salt is excreted in urine, Cl- remains in ECF, treatment with NaCl leads to hyperchloremia

Question 11

Ketone strips?

Answer 11

nitroprusside reaction turns purple in presence of AcAc, in ketoacidosis BOHB:AcAc ratio goes from 1:1 up to 5.5:1 meaning strips can underestimate ketonaemia

Question 12

DKA diagnosis?

Answer 12

caused by lack of insulin + stress (for counter-regulatory activation): hyperglycaemia, decreased venous pH, high bicarb, ketonemia or ketouria

Question 13

K+ feedback vs feedforward?

Answer 13

effective but slow overshoot (aldosterone increasing renal excretion and cell uptake) vs. rapid anticipatory

Question 14

What controls K after a meal??

Answer 14

insulin activates ATPase (not GLUT4 linked, glucose and amino acid consumption stimulates K shift), glucagon & cAMP stimulation in protein consumption

Question 15

Other controls of K movment?

Answer 15

B2 adrenergic stimulaiton (shift into cells, B blockers linked to hyperkalaemia), acidosis, exercise and cell lysis (both shift out of cells), increased/decreased osmolality e.g. diabetes

Question 16

Reabsorption proportions of kidney?

Answer 16

proximal 65%, loop 25-30%, 4% in CD, net excretion > absorption

Question 17

Factors of K secretion?

Answer 17

ATPase on basolateral membrane, luminal membrane permeability, electrochemical gradient from lumen -> blood

Question 18

Increasing distal secretion?

Answer 18

increased s[K] (non-linear, increase ATPase activity, stimulates aldosterone), aldosterone (linear), increased distal tubular flow rate (decreased conc., increased gradient between lumen and blood, opposite in renal impairment) NB: acidosis decreases