Endocrine emergencies Flashcards
Discuss the pathophysiology, clinical signs and diagnostic investigation of diabetic
ketoacidosis (DKA)
PATHOPHYSIOLOGY OF DKA;
DKA is a complication of diabetes mellitus. In dka there is a degree of insulin resistance and the production of ketones results. The insulin resistance occurs due to some imbalance b/n glucagon, adrenalin,cortisone and growth hormone.Usually ,as well as diabetes, there is some other underlying dz. 90% of cats with dka have concurrent dz, and is usually hepatic lipidosis, chronic renal failure,pancreatitis, or bacterial/viral disease.
70% of dogs with dka have concurrent dz eg pancreatitis,uti, hyperA or heart dz.
In summary, there is lipolysis, and production of ketones and metabolic acidosis, glucosuria and osmotic diuresis, gluconeogenesis & glycogenolysis.
Usually see hyponatraemia due to v+/d+, compensatory polydipsia further diluting , and a pseudo hyponatraemia due to hyperglycaemia osmotically drawing water from intracellular to extracellular space. To account for the pseudohyponatraemic effect,
the actual sodium=measured Na mmol/L PLUS
1.6(measured glucose mmol/L-normal glucose mmol/L)/5.55
Usually have hypokalaemia but might measure normal due to ongoing urinary loss. Also beware that once start adding insulin, this results in potassium moving into intracellular space (driven by glucose) and potassium levels fall and often require supplementation (as well as being further diluted with fluid therapy).
Sometimes have hypophosphataemia and if so might supplement with potassium phosphate (to supplement both potassium and phosphate).
May have hypomagnesaemia, usually only supplement if there has also been hypokalaemia and this has not responded to supplementation.
In DKA, the hormones are acting thus:
1.Insulin:Stimulates glucose uptake into cells
Stimulates glycogen synthesis and fatty acid conversion to triglycerides for storage
Decreases lipolysis, gluconeogenesis, glycogenolysis and proteolysis
Causes increased movement of potassium intracellularly
2. Glucagon;Promotes glucose and FFA formation
Inhibits insulin
Stimulated by absence of insulin and cellular glucose demand
3. Adrenalin (catecholamine);Inhibits insulin release
Promotes fat and protein production as well as glycogen breakdown
4. Cortisol;Promotes glycogen and protein breakdown for glucose production
Inhibits insulin
5. Growth hormone;Enhances lipolysis
Blocks insulin action in peripheral tissues. (note growth hormone is still produced by the pituitary in adults, just in less quantities than juveniles)
CLIN SIGNS; may have chronic weight loss pu/pd and polyphagia, may have acute v+, abdo pain, depression, dehydration/hypovolaemic shock, sometimes tachypnoea, sometimes slow deep resp in severe ketosis, may have liver dz with jaundice etc etc.
DIAGNOSTIC INVESTIGATION;
dka confirmed with persistent fasted elevated bg, ketonaemia (beta hydroxybutyrate)and acidosis, and ketonuria. Rest is searching for or ruling in/out accompanying dz. (esp liver, pancreatitis and uti and hyperA but there are others).
Describe the clinicopathological abnormalities and management regimes for DKA
patients
If diabetes but not in dka, not emergency. Dka always an emergency (and thus best be in 24 hour care). Note that diabetes mellitus might be Primary (absolute insulin deficiency as reduction of insulin secretion from pancreatic beta cells), or Secondary (relative insulin deficiency due to loss or inactivity/blockage of insulin receptors).
STAGES of dka management;(some overlap with timing depending on case)
1.Correct fluid and electrolyte imbalances.This does not reduce ketogenesis, but does reduce diabetogenic hormone production, restore kidney filtration and correct electrolyte derangements and dehydration. Usually go for plasmalyte 148 or hartmann’s. Studies have now shown no worse effect if start insulin at same time as fluids (although probably might be better to wait a few hours if not able to do close monitoring or insulin cri etc). Treat hypovolaemia with boluses 5-10ml/kg. Once re-perfusion parameters met, adjust per elctrolytes and check electrolytes/lactate etc every 4-6 hours.
2.rapid acting insulin
Rapid-acting regular crystalline insulin CRI
▪ CRI of 0.05 IU/kg/hr for cats or 0.1 IU/kg/hr for dogs. This can be achieved by:
* Addition of 2.2 IU/kg for dogs or 1.1 IU/kg for cats to 250mls of
0.9% saline and give 10ml/hr
* OR addition of 25 IU to 500ml of 0.9% saline and run at
1ml/kg/hr (up to 2ml/kg/hr for dogs)
▪ Once the BG is <12-14 mmol/L, halve the insulin infusion rate and add dextrose to fluids to a concentration of 2.5-5%
▪ NB: Flush the infusion fluid line with the insulin solution before administration as insulin absorbs into plastic
3. anti-emetics/pain relief supportive care and diagnostics as req
4.out of dka onto long acting insulin.
PROGNOSIS
* 70% of dogs and cats with DKA survive to discharge. Both complications of DKA and
concurrent illness contribute to mortality.
* 7% of dogs and up to 40% of cats will have recurrent episodes
* Median hospitalisation time is 5-6 days
Discuss hyperglycaemic hyperosmolar syndrome (HHS)
complication of diabetes mellitus but has no ketosis. Thought there is just enough insulin present to prevent ketosis.BG elevated and serum osmolarity elevated(>350mOsm/kg) Note Normal serum osmolarity = 2Na + glucose + BUN. = ~300
There are Hormonal alterations – epinephrine, glucagon, cortisol and growth hormone →
hyperglycaemia as primary result
Correct fluid and electrolyte derangements gradually. Wait for fluid corrections to occur before starting insulin.
Frequently have concurrent dz also eg renal failure, chf, pancreatitis, infection, neoplasia.need to treat these also.
Calculations
o Na corr) = Na+ meas + 1.6 ({measured glucose – normal glucose} /100)
o Osmolality serum osm = 2(Na) + (Bun /2.8) + (glucose /18)
o Effective osmolality = 2(Na) + (glucose /18)
o For every 100mg/dl increase in glucose above normal, measured Na decreases by 1.6mEq/dl.
Outline the pathophysiology of glucose regulation and the clinical signs, diagnostic
investigation and management of patients with hypoglycaemia
PATHOPHYSIOLOGY;
Glucose is main energy source for ATP. Glucose obtained via:
a)Intestinal absorption from digestion of carbohydrates
b)Breakdown of glycogen to glucose via glycogenolysis
c)Production of glucose from precursors lactate, pyruvate, amino acids and glycerol via gluconeogenesis
* Balance between glucose lowering hormones (insulin) and glucose elevating hormones (primarily glucagon, epinephrine, cortisol and growth hormone)
INSULIN;Secreted by beta cells in pancreas in response to rising concentrations of glucose (also amino acids and gastrointestinal hormones present after a meal)
o Via
* Passage of glucose into cells
* Produces ATP
* Glucose into glycogen into the liver (glycogenesis) and storage of glycogen
* Conversion of fatty acids into fat (lipogenesis), storage of fat
* Conversion of fatty acids to ketone bodies are inhibited by insulin
* Protein synthesis and inhibits protein catabolism
GLUCAGON;produced by alpha cells of islets of Langerhans in pancreas
* Glucagon increases glucose concentrations in the blood (hyperglycaemic agent)
* Via
o Promotes glycogenolysis (glycogen to glucose)
o Formation of new glucose from non-carbohydrate sources such as amino acids, fatty acids and lactic acid (gluconeogenesis)
o Release of glucose in blood stream by hepatocytes
o In adipose tissue stimulates fat breakdown into fatty acids
ADRENALINE: Limits insulin
* Increases glucagon
CORTISOL; * Increase glucose facilitating lipolysis
* Release of amino acids from muscle for gluconeogenesis in the liver
GROWTH HORMONE;* Antagonistic effect of insulin by decreasing peripheral glucose utilisation
* Promoting lipolysis
DURING period of inadequate dietary intake or if blood glucose is low, the following
takes place:
o Inhibition of insulin
o Increased glucagon, adrenalin, growth hormone and cortisol secretion
o Glycogenolysis, lipolysis and increased amino acid mobilisation
o Decreased glucose utilisation by cells
o Gluconeogenesis
Hypoglycaemia occurs when these counterregulatory systems fail
CLIN SIGNS
At bg <2.8 mmol/L may see activation of sympathetic nervous system and pacing, vocalisation, restlessness, trembling, shaking, vomiting, tachypnoea,
diarrhoea, urination, bradycardia.
At bg <2mmol/L get neuro signs with brain affected (brain is 100%reliant on glucose for energy source) and may see altered mentation, drowsiness, weakness, ataxia, seizures, coma.Permanent brain injury/death if prolonged.
DIAGNOSTIC INVESTIGATION;Establishing that hypoglycaemia is the cause of a patient’s clinical signs requires the
satisfaction of three criteria called Whipple’s Triad
o Clinical signs of hypoglycaemia
o Low measured blood glucose
o Improvement with return to normoglycaemia
* If the cause of hypoglycaemia is not immediately evident, further diagnostics are
directed at identifying concurrent or predisposing illness.
Test fasted bg and endogenous insulin.
* CBC/biochemistry/UA
o Inflammatory/infectious markers
o Liver failure markers
* Urea, cholesterol, albumin, glucose
* Coagulopathy markers (PT, aPT)
* Imaging
o Adrenals - size
o Source of infection
o Neoplasia
* Collect blood for insulin measurement as well as glucose measurement (note: must be
during hypoglycaemic event)
* ACTH stimulation test if concerned hypoadrenocorticism
CAUSES OF HYPOGLYCAEMIA;
1. Increased insulin;ddx iatrogenic, insulinoma, other-insulin-secreting tumour, drugs.
Insulinoma of beta secreting pancreatic cells. Usually malignant and already spread. Tx with sugery, low sugar foods, steroids and diazoxide.
Other-insulin-secreting tumours (or insulin-like-secreting)include leiomyoma, leiomyosarcomas,
lymphoma, adenocarcinoma, hemangiosarcoma, plasmacytoid tumour, oral
melanoma and other adenocarcinomas.
Drugs: Xylitol stimulates insulin release from pancreas and can cause hepatic necrosis resulting in severe hypoglycaemia
B-blockers can cause hypoglycaemia due to adrenergic counter regulatory
mechanisms
- Excessive glucose utilisation
eg Infection/sepsis/SIRS (common)
o Increased cellular consumption, impaired gluconeogenesis
o Usually also have decreased intake and decreased hepatic function
o Increased glucose consumption with neoplasia
o Prolonged seizure activity - Decreased production
Hepatic failure
o Hypoglycaemia due to hepatic failure means there is > 70% loss of hepatic function
o Dysfunction of glycogen storage, glycogenolysis and gluconeogenesis pathways occurs
o Other signs of hepatic failure will be present – lethargy, inappetence, coagulopathy, GI signs, jaundice
Neonates / toy breeds Hypoglycaemia of neonates and toy breeds (common)
o May have immature hepatic enzymes
o Low glycogen stores and inadequate substrates
o Have increased renal glucose loss up to 3 weeks of age
o Predisposing factors in neonates include:
▪ infection, vaccination, exercise, GI disease, poor nutrition
o Consider also inherited or congenital abnormalities
▪ PSS, hepatic disease, glycogen storage disease and counter regulatory hormone deficiency - Endocrine abnormalities
Hypoadrenocorticism (common)
o Loss of cortisol counter regulator mechanism
o Glucocorticoids are needed for hepatic production of glucose
TREATMENT
o Dextrose - administer IV dextrose - 0.5-1ml/kg (0.25-1g/kg) of 50% dextrose
▪ Diluted at least 1:3 or 1:4 with saline
▪ Given IV over 5 minutes as it is hyperosmotic and can cause phlebitis
▪ Repeat until euglycaemic
▪ If the patient has normal mentation at this point, small frequent meals
should be offered of a food low in simple sugars
▪ If oral feeding is not possible or hypoglycaemia is more difficult to
control:
* 2.5-10% dextrose CRI (supplementation to IV fluids) –
50ml of 50% glucose in 1000ml of fluids = 2.5%
100ml of 50% glucose in 1000ml of fluids = 5%
**10% dextrose CRI should be administered via central line
* CRIs should be weaned slowly whilst ensuring continued
euglycaemia
**10% dextrose CRI should be administered via central line
▪ Avoid excess dextrose administration especially in hypoglycaemia of
insulinoma as severe rebound hypoglycaemia can occur
* Glucocorticoid
o Antagonises insulin and stimulates gluconeogenesis - may help with
paraneoplastic or endocrine induced hypoglycaemia
o Contraindicated in patients with infection/sepsis
Dexamethasone 0.05-0.1 mg/kg IV
Prednisolone 0.25-0.5 mg/kg PO q12 for insulinoma
* Glucagon can be considered if the 5% glucose and glucose boluses are not enough to
maintain a euglycaemia (refractory hypoglycaemia), although this is rare.
o Glucagon (Australia) comes as a 1mg vial and is reconstituted with supplied
diluent
Add the above to 1L of 0.9% NaCl to get 1000ng/ml Glucagon solution
Dose is 50ng/kg IV as a bolus dose (use an insulin syringe)
Follow with CRI of 5-10 ng/kg/min (up to 40ng/kg/min)
Use lowest possible rate to achieve euglycaemia
Usually 24-36 hours are required in cases of large insulin overdose
Wean glucagon CRIs slowly while monitoring for continued euglycaemia or
hyperglycaemia
* Seizure control may be necessary if not responsive to treatment of hypoglycaemia
o Diazepam 0.1-1mg/kg IV
16
* Mannitol may be needed if elevated ICP is suspected
o Clinical signs include loss of consciousness, opisthotonos, pupillary dilation,
bradycardia and hypertension. Consider especially if these signs occur after
euglycaemia has been achieved
o 0.5g/kg slow IV over 30 minutes (an in-line filter needs to be used).
Remember if due to exogenous insulin administration to watch out for electrolyte disturbances too.
Discuss the pathophysiology of primary and secondary hypoadrenocorticism
PRIMARY HYPOADRENOCORTICISM;
Most common form in dogs(95% of cases) There is bilateral loss of >90% of adrenal gland cortices. Usually both mineralocoid and glucocorticoid deficiency. Most typically due to some kind of autoimmune destruction, but may also occur due to neoplasia, idiopathic, iatrogenic (eg mitotate) or infectious.
“Atypical Addisons”= primary hypoA but with normal electrolytes (up to 30% of primary cases).
SECONDARY HYPOADRENOCORTICISM;dysfunction occurs at level of hypothalamus (produces corticotropin releasing hormone), or at level of pituitary (produces adrenocorticotropic hormone). Results in reduced CRH and or ACTH secretion leads to atrophy of adrenal cortices and glucocorticoid deficiency (not usually mineralocorticoid). The dysfunction may be due to neoplasia, surgery. May also be iatrogenic due to steroid use.
Describe the common clinicopathological abnormalities and diagnostic investigations
for hypoadrenocorticism
CLIN SIGNS OF HYPOADRENOCORTICISM;
May include v+/d+, weakness, acute collapse (esp if mineralocorticoid deficiency),hypovolaemic shock,vague waxing/waning, anorexia, pupd, abdo pain. BradycardiaRarely hypoglycaemic seizure. Often episode triggered by a stressor.
LAB; low sodium, high potassium (Na/K ratio <24 is suspicious and if <17 is very suggestive).[note low Na/K ratio also may occur in gi dz (whipworm/parvo) and cardiac dz/body cavity effusions].
Normo-hypoglycaemia. Hypercalcaemia sometimes (cortisol required for urinary excretion of calcium).
Absence of stress leukogram.Non regenerative anaemia.Sometimes there are liver changes which resolve with tx of addisons.
Low urine sg. Hypovolaemia, occasional megaoesophagus. Small adrenal glands (left adrenal gland <3.2mm is strongly suggestive).
Low baseline cortisol (if normal, hypoA is excluded).. ACTH stim test required for definitive dx.(pre acth and post acth samples both show cortisol lower than normal baseline, = hypoA.) Prior glucocorticoids,trilostane,mitotane or ketoconazole can interfere with test. Does not distinguish b/n primary or secondary hypoA. To distinguish b/n, need endogenous ACTH, which is above normal in primary hypoA, and below normal in secondary hypoA. (very specific sample requirements though)
Discuss the emergency treatment and management of patients in ‘Addisonian Crisis’
Fluid bolus for shock hypovolaemia. If sodium <120mmol/L will need to slowly correct. Correct hypoglycaemia and anaemia. Monitor electrolytes and ecg. If highly suspicious of addisons but not yet confirmed, can give dexamethasone 0.05-0.1mg/kg i/v.
Once dz confirmed, (or acth test is underway), can give Hydrocortisone 1.25mg/kg i/v ONCEonly then 0.5-1mg/kg/hr cri OR 0.1-1mg/kg i/v q6hours then taper off
or
dexamethasone phosphate 0.05-0.1mg/kg i/v then 0.025mg/kg i/v q12hours then taper off.
Other suportive tx eg anti-emetics etc as req.
AFTER initial crisis over:
MINERALOCORTICOID SUPPLEMENTATION
Deoxycortisone pivalate 1.5-2.2mg/kg i/m or s/c q25 days(range q15-34days)
OR
Fludrocortisone 0.01-0.02mg/kg po sid (or divided and given bid). (has some slight glucocorticoid activity too which is sometimes sufficient)
PLUS GLUCOCORTICOID SUPPLEMENT USUALLY REQUIRED
Prednisolone 0.05-0.2mg/kg sid or eod. Taper to lowest effective dose controlling signs.
Discuss Critical Illness Related Corticosteroid Insufficiency Syndrome (CIRCS)
Still not fully understood. Some patients with pressor -resistant septic shock hypotension, respond to 1-4.3mg/kg hydrocortisone daily but divided into 4 doses over 24 hours or as cri. The response concludes the diagnosis .
