ENDO 2 Flashcards
What does ketoacidosis refer to?
Metabolic acidosis in presence of ketones and low bicarb
Action of insulin:
Released in response to high blood sugar.
Cells absorb glucose from blood to use as fuel.
Muscle and liver use it in glycogenolysis.
Action of glucagon:
From alpha cells.
Released in response to low blood sugar, and breaks down glycogen stores (glycogenolysis).
Also gluconeogenesis, glucose from proteins and fat conversion.
When are ketones produced?
Glycogen stores have been deplete, insufficient glucose supply e.g. prolonged fasting.
They are made from fatty acids, and are water soluble and can cross BBB.
Kidneys usually buffer ketones (using bicarb), but cannot do this in extreme hyperglycaemic ketoacidosis i.e. DKA.
4 clinical / biochemical features of DKA:
Hyperglycaemia
Ketosis
Dehydration
Serum potassium normal or high, but total body potassium is low.
Insulin and potassium relationship:
Insulin drives potassium into cells, so when insulin treatment starts, can cause severe hypokalaemia (serum).
Diagnostic criteria for DKA:
Glucose >11 or known DM
pH <7.3
Bicarb <15
Ketones >3 or urinary ketones +++
Precipitating factors for HHS:
Illness
Sedative drugs
Dementia
Biochemical findings in HHS:
As comes on more insidiously over a few days can be more marked derangement:
Hyperglycaemia >30mmol/L
Serum osm raised >320
Ketones <3
Bicarb >15
pH >7.3
Hypovolaemia
Differentiating between T1DM and MODY:
C-peptide levels are low in T1DM
Normal / elevated in MODY
Measure fasting C-peptide
Types of MODY and their respective mutations and prognoses:
GCK Mutation; MODY2, mild stable fasting hyperglycaemia, rare to develop severe complications.
HNF1A mutation: MODY3, progressive hyperglycaemia, higher risk of complications e.g. retinopathy, nephropathy, CV disease etc.
Others:
MODY1 = HNF4A
MODY4 = PDX1
Treatment depends on specific subtype.
Features of excess prolactin in men and women:
Men: gynaecomastia, impotence, loss of libido
Women: galactorrhoea, amenorrhoea (secondary)
Pregnancy induces raised prolactin; how does the body compensate for this so the woman does not lactate until after she has given birth?
Progesterone inhibits the effects of prolactin in breast tissue.
Progesterone is HIGH in pregnancy, and falls rapidly after delivery, allowing lactation at the appropriate time.
Treatments that lower total body potassium;
Calcium resonium (reduces potassium absorption in GI tract, slow and causes constipation)
Loop diuretics e.g. furosemide, bumetanide
Haemodialysis
Other management includes stopping exacerbating drugs e.g. ACEi, spiro, ARB, NSAIDs, treating underlying cause.
What electrolyte abnormality is present with Trousseau’s and Chvostek’s sign, and what are they both?
Hypocalcaemia
Trousseau = carpal spasm if brachial artery occluded with BP cuff, wrist flexion and fingers drawn together.
Chvostek = parotid tap causes facial muscles to twitch
Mechanisms of how malignancy can cause hypercalaemia:
PTHrP secretion e.g. lung cancer
Bony mets
Myeloma –> increased bone resorption caused by inflammatory cytokines from the myeloma cells.
MEASURE PTH IN PATIENTS WITH HYPERCALCAEMIA
Features of acromegaly:
Coarse facial appearance, spade hands, big shoe size
Large tongue, interdental spaces
Excessive sweating and oily skin due to sweat gland hypertrophy
Pituitary tumour features - hypopituitarism, headaches, bitemporal hemianopia.
Raised prolactin in 1/3
MEN-1 in 6%
Complications of acromegaly:
Hypertension
Diabetes >10%
Cardiomyopathy
Colorectal cancer
Investigating acromegaly:
Serum IGF-1, can also be used to monitor disease.
OGTT used to be used first line.
GH normally suppressed in hyperglycaemia, but in acromegaly there is no suppression of GH.
Criteria for DKA resolution:
pH >7.3
Bicarb <15
Serum ketones <0.6
Eating and drinking - start SC insulin again
If not resolved within 24 hours, senior endo review, also if this has never happened before.
Complications of DKA:
Gastric stasis
VTE
Arrhythmia secondary to potassium
Incorrect fluid therapy - cerebral oedema (particularly young adults and children, need slower fluid replacement, usually presents 4-12 hours post treatment start with irritability, visual disturbance, focal neurology etc), hypokal, hypoglyc
ARDS, AKI
Classical result in high dose dex suppression test in Cushing’s disease vs. syndrome vs. ectopic ACTH syndrome.
Disease = ACTH AND CORTISOL suppressed.
Syndrome = cortisol not suppressed, ACTH suppressed. Due to e.g. adrenal adenoma.
Neither suppressed = ectopic ACTH.
What is pseudo-Cushing’s?
Mimics Cushing’s disease, often due to alcohol excess or severe depression.
Causes false positive dexamethasone suppression test or 24hr urinary free cortisol. Insulin stress test to differentiate.
What does calcitonin do?
Secreted by parafollicular C cell.
Reduces calcium levels in the blood, reverse effect of PTH.
Inhibits osteoclast activity and calcium reabsorption in the kidneys.
Can be given IM or SC to treat hypercalcaemia caused by malignancy.
What is pseudohypoparathyroidism?
Target cells insensitive to PTH.
Low IQ, short stature, shortened 4th and 5th metacarpals.
Low calcium. but high phosphate and high PTH.
What does alfacalcidol do?
Vitamin D analogue
What does cinacalcet do?
Lowers PTH in patients with hyperparathyroidism.
Mimics calcium action on CaSR in PT glands, reducing PTH release from the chief cells.
2 basic biochemical problems in CKD:
1-alphahydroxylation normally occurs in kidneys = LOW VITAMIN D in CKD. Causes low calcium due to lack of vitamin and high phosphate.
Kidneys normally excrete phosphate = HIGH PHOSPHATE in CKD. This drags calcium from bones, resulting in osteomalacia.
Classification of prediabetes with HbA1c and fasting glucose levels:
HbA1c 42-47
Fasting glucose 6.1-6.9
Intensive weight loss, increased exercise and change in diet can prevent / delay progression to diabetes.
Two types of impaired glucose regulation:
Impaired glucose tolerance - due to muscle insulin resistance. More likely to develop T2DM and CV disease.
Impaired fasting glucose - due to hepatic insulin resistance.
