1
Q
What are the two major types of tissue in the pancreas
A
Acini and langerhans
Acini produces digestive juices and Langerhans insulin and glucagon
2
Q
What do the alpha and the beta cells on the Langerhans tissue in the pancreas produce
A
Alpha: glucagon and somatostatin
Beta: insulin, amylin
3
Q
Give an example of an enzyme linked receptor
A
Insulin receptor
4
Q
State 4 main effects of insulin
A
Glucose transport: increased uptake into muscle cells and adipose tissue. Glucose transport protein translocated and then binds to cell membrane and facilitate glucose uptake by the cells
Protein synthesis
Glycogen syntheses
Growth and gene expression
Increased cell membrane permeability to amino acids, K, P
Change on state of phosphorylation of many intracellular enzymes
5
Q
Where does GLUT 4, GLUT 1, GLUT 2 have its main effects?
A
Muscle GLUT 4
Brain GLUT 1
Adipose tissue GLUT 4
Beta cells pancreas: GLUT 2
6
Q
What enzyme causes hydrolysis of triglycerides already stored in fat, and why does it matter in DKA
A
Hormone-sensitive lipase. Inhibited by insulin. When inhibited release of fatty acids into the blood from the fat cells is inhibited. if no insulin (DKA), more fatty acids are released as they are needed as energy source. Important in ketongenesis. Hormone-senistive lipase is also stimulated by adrenalin
7
Q
How does glucose stimulate b cells of the pancreas to produce insulin
A
Glucose enters via GLUT 2 receptor. Glucose via glucokinase to glucose 6 phosphate. Then oxidation. This closes the ATP K channel and the depolarization opens Ca channel. Ca releases insulin vesicles (Guyton fig 79-7)
8
Q
Give 7 factors that increase insulin secretion and 4 that decrease
A
Increase:
Increased blood glucose
Increased blood free fatty acids
Increased blood amino acids
GI hormones (gastrin, cholecystokinin, secretin, GIP)
Glucagon
Growth hormone
Cortisol
Parasympathetic stimulation/acetylcholine
B adrenergic stimulation
Insulin resistance, obesity
Sulfonylurea drugs (glybride, tolbutamide)
Decrease insulin secretion:
Decreased blood glucose
Fasting
Somatostatin
Alpha adrenergic activity
Leptin
9
Q
What hormone causes breakdown of glycogen (glycogenolysis) and increased gluconeogenesis in the liver
A
Glucagon
10
Q
By which 3 processes is cellular energy generated
A
Glycolysis, tricarboxylic acid (krebs cycle), the electron transport chain/oxidative phosphorylation
11
Q
How many mol ATP does 1 mmol of glucose make
A
38-36 mol ATP (36 coincidental the same as p50 for cats)
12
Q
What is the glucose renal threshold in dogs and in cats
A
- Cat 15 mmol/l
- Dog 10-12 mmol/L
13
Q
For every 1 mmol of glucose, how much will Na decrease? And for every 100 mg/dl glucose
A
For 1 mmol of glucose: 0.3-0,4 mmol/l
For every 100 mg/dl: 1.6 mEq/l
14
Q
What are the main products of glycolysis
A
A mmol glucose becomes 2 mole ATP, 2 mole NADH, 2 mole pyruvate
15
Q
Give 3 secondary reasons for diabetes mellitus
A
Hypersomatotropism, hyperadrenocorticism, exogenous glucocorticoids, dioestrus, pregnancy in dogs
16
Q
What is glucotoxicity
A
beta cell damage caused by persistent hyperglycemia and reversible if caught early, especially in cats
17
Q
what concurrent disease are seen in dogs and in cats with DKA
A
- Dogs: pancreatitis, UTI, neoplasia, hyperadrenocorticism
- Cats: hepatic lipidosis, cholangiohepatits, pancreatitis, bacterial and viral infections, neoplasia
18
Q
What are the main counterregulatory hormones in DKA 4p
A
Glucagon, cortisol, catecholamines, growth hormone
19
Q
What are the three main enzymes that control the rate of ketogenesis
A
Hormone-sensitive lipase (break down triglycerides to fatty acids) – no inulin to inhibit the enzyme. Glucagon will stimulate.
Acetyl CoA carboxylase (convert acetyl CoA to malonyl Coa – malonyl CoA blocks fatty acids transport into mitochondria) – no insulin to make malonyl, there is no blockade. Glucagon will inhibit the making of malonyl, there is no blockade
Mitochondrial HMG CoA synthase (converts acetoacetylCoA into acetoacetate) – no insulin to inhibit the enzyme. Glucagon will stimulate
20
Q
What does insulin do to gluconeogenesis, glucagon secretion, protein synthesis, glycogen
A
Inhibits gluconeogenesis (as wants to amino acids for protein synthesis)
Inhibits glucagon secretion
Promotes protein synthesis
Stimulated glycogen synthesis
21
Q
Increase insulin resistance. Activates glycogenolysis and glucogenesis. Activates lipolysis. Inhibits insulin secretion
Epinephrine
Glucagon
Cortisol
GH
A
Epinephrine: Increase insulin resistance. Activates glycogenolysis and glucogenesis. Activates lipolysis. Inhibits insulin secretion
Glucagon: Activates glycogenolysis and glucogenesis
Cortisol: Increase insulin resistance. Activates glycogenolysis and glucogenesis
GH: Increase insulin resistance. Activates lipolysis. Inhibits insulin secretion
22
Q
Is there any clear sex predisposition in DKA in dogs
A
- No clear breed or sex predisposition, although one retrospective study reported an overrepresentation of intact female dogs comprising 43% of its DKA patient
23
Q
Give two risk factors for DKA in dogs and cats
A
dogs: concurrent disease (pancreatitis, UTI, hyperadrenocorticism, neoplasia),
cats: concurrent disease (IBD, acromegaly, hepatic lipidosis, CKD, pancreatitis, bacterial or viral infections, neoplasia), glucocorticoids, B-blockers, furosemide
24
Q
what ketone does urine reagent strip react to and can this be changed in any way
A
acetoacetate and to lesser extent acetone
3% hydrogen peroxide to promote conversion to b-hydroxybuturate but study show does not improve detection
Plasma or serum from microhematocrit tube on urine regent strip has better sensitivity and specificity than urine
25
What is the mechanism behind a false neg and false positive ketone urine reagent strip and what % of ketones are missed in cats
False neg due to there being b-hydroxybuturate and not acetoacetate, acidosis pushed the ketone production towards b-hydroxybuturate
During tx the B hydroxybutyrate improves but acetoacetate plateau for a bit. The nitroprusside test will measure the acetoacetate that is still high which could lead to dangerous increase of insulin tx
Urine dipstick miss 12% of DKAs in cats
26
What is the % of dogs that have increased alp in DKA
97%
27
What is the mechanism behind hypoK in untreated DKA
o Hyperglycaemia and hyperosmolality lead to shifting of water, K, P, and Mg from the intracellular to the extracellular space. Glucosuria-induced osmotic diuresis subsequently causes significant urinary water and electrolyte losses leading to dehydration, hypovolemia, and total body K, P, and Mg depletion
o As volume depletion and acidosis progress, decreased renal perfusion, renal excretion, and hypoinsulinemia may make extracellular K, P, and Mg concentrations appear normal in untreated DKA
o Acidosis can further contribute to normal extracellular K concentration due to shifting of K to the extracellular space in exchange for hydrogen ions.
o In intercalated disk with apical H+/K+ ATPase (eller??)
28
What % pf dogs with DKA gets a reduction in K and what % in P after insulin tx is started for DKA
K 84% of dogs, P 48% of dogs
29
What are the most life-threatening complications of hypoK and hypoP
muscle weakness, respiratory paralysis, cardiac conduction abnormalities, and haemolysis
30
what are the mechanisms behind hypoNa in DKA. 3 p
Free water retention because of hypovolemia-induced ADH release and urinary Na losses likely contribute to the development of hypoNa but the degree of hyperglycaemia has to be taken into account when assessing its severity.
31
What % of DKA has a negative urine culture and what is the most common reported bacterial isolate
Urine culture NEGative in 87%, e coli most common
32
State 5 differentials for ketonemia
- DKA
- acute pancreatitis
- starvation
- low-carbohydrate diet
- persistent hypoglycaemia
- persistent fever
- pregnancy
33
Justify why you pick fluid containing bicarbonate precursor over 0.9% saline in a DKA px
Fluids containing bicarbonate precursors appear to aid in faster resolution of metabolic acidosis and decrease the incidence of hyperCl, which has been associated with negative effects such as increased time to DKA resolution, risk of AKI, and increased hospital length of stay.
hypoNa normally corrects itself when hyperglycaemia and hyperosmolality decreases
34
what rate should no be exceeded during K iv supplementation
0.5 mEq/kg/h
35
Why is the recommended iv regular insulin dose in dka lower in cats than dogs
due to suspected higher risk for neurologic adverse effects from rapid correction of hyperglycaemia However, a recent study treating cats with the canine insulin dosage of 2.2 U/kg/day did not show an increased frequency of adverse neurological or biochemical events when using a sliding scale to limit the amount of insulin the cats received
36
state 2 reasons for dogs and 2 for cats for reduced survival to discharge in DKA
- Dogs with concurrent hyperadrenocorticism, lower Ca, anaemia, and more severe acidosis
- Cats with more severe azotemia, metabolic acidosis, and hyperosmolarity
37
What % of dogs and % of cats experience recurrent DKA after hospital discharge
17% of dogs and 42% of cats
38
What is the formula for bicarbonate supplementation
0.3 x BW (kg) x base deficit
39
What is the definition of hyperglycemic hyperosmolar syndrome (with numbers)
Hyperglycaemic hyperosmolar syndrome (HHS) is an uncommon form of diabetic crisis marked by:
- severe hyperglycaemia (>600 mg/dl, 33.3 mmol), -minimal or absent urine ketones
-serum osmolality more than 350 mOsm/kg in cats and >325 in dogs.
40
What are the three main alterations behind hyperglycemic hyperosmolar syndrome
Hormone alterations, reduction in GFR, contributions from concurrent disease
41
Why is fluid replacement before insulin administration more important in HHS than DKA
In HHS: As intravascular glucose and osmolality decline, vascular volume is anticipated to decrease as water moves to the interstitium and intracellular space. As such, administration of insulin prior to adequate fluid resuscitation can contribute to cardiovascular collapse and death – replace vascular volume
42
What is associated with poorer outcome in dogs with HHS
Abnormal mental status and low venous pH
43
What is the mortality rate in dogs and in cats with HHS
Cats 65%, dogs 38%. Only 12% cats survive > 2 months
44
What % of dogs and cats presenting to an OOH emergency centre with coma or stupor with an identified cause had hypoglycemia
10% dogs, 6,6% cats
45
What are the 3 main sources of glucose
- intestinal absorption of glucose from digestion of carbohydrates
- breakdown of the storage form of glucose (glycogen) via glycogenolysis
- production of glucose from precursors lactate, pyruvate, amino acids, and glycerol via gluconeogenesis.
46
Give examples of the hormone dependant mechanism for glucose control and the non hormone dependant mechanisms (2 each)
hormonal: insulin, glucagon, epinephrine, cortisol, growth hormone
non hormonal: autonomic nervous system; input from GI tract, brain, heart, liver etc
47
insulin is secreted in response to what 4 stimuli?
- glucose
- amino acids
- gastrointestinal hormones (gastrin, secretin, cholecystokinin, glucagon-like peptide-1, gastric inhibitory peptide) present after a meal
- sensory signals from mastication, taste, and even the anticipation of eating
48
what hormone does all of these: Inhibits gluconeogenesis and glycogenolysis, promotes glycogen storage, stimulates glucose uptake and utilization by insulin sensitive cells, and decreases glucagon secretion, promotes triglyceride formation in adipose tissue and the synthesis of protein and glycogen in muscle.
insulin
49
What is neuroglycopenia and how do you diagnose it
hypoglycaemia of the CNS
- altered mentation or dullness, lack of response to stimuli, sleepiness, weakness or recumbency, ataxia, blindness or altered vision, and seizures.
- If prolonged can lead to permanent brain injury and neurologic signs, especially blindness, that persist beyond resolution of the hypoglycaemia.
Neurogenic signs result from activation of the adrenergic system in response to the hypoglycaemia
Diagnosis
- 60 mg/dl (3.33 mmol) or less
o clinical signs often do not develop until the level is less than 50 mg/dl (2.8 mmol).
- Whipple’s triad provides guidelines for identifying hypoglycaemia:
o clinical signs consistent with hypoglycaemia,
o a low blood glucose level
o abatement of signs with correction of the hypoglycaemia
50
what is whipples triad?
- Whipple’s triad provides guidelines for identifying hypoglycaemia:
o clinical signs consistent with hypoglycaemia,
o a low blood glucose level
o abatement of signs with correction of the hypoglycaemia
51
causes of hypoglycaemia? 4 big groups and minimum 2 examples in each group (saccm box 75.1)
excess insulin or insulin analogue
- exogen insulin overdose
- insulinoma
- paraneoplastic syndrome
- toxins and medications
excess glucose utilization
- infection
- exercise-induced hypoglycaemia
- seizure activity
- paraneoplastic
- polycythaemia
- leucocytosis
- pregnancy
- anaphylaxis
artifact
- pseudohyperglycemia
- handheld glucometer
decreased glucose production
- neonatal hypoglycaemia
- hepatic dysfunction
- Hypocortisolism
- counterregulatory hormone deficiency
- glycogenic or gluconeogenic enzyme deficiency
- anaphylaxis
- B blockers
52
State 3 medical uses for insulin
- Diabetes mellitus
- Hyperkalaemia
- Ca channel blocker overdose (ex amlodipine, diltiazem)
53
3 ways of aiding diagnosing insulinoma
- Blood insulin when hypoglycemia (can do calculated amended insulin/glucose ratio AIGR= (insulin x 100) / ((plasma glucose mg/dl -30). >30 suggest insulinoma
- Fructosamine
- Provocative testing
o Glucagon tolerance testing
o Oral glucose tolerance test
o Tolbutamide tolerance test
o Epinephrine stimulation test
- AUS
- CT
- MRI
- scintigraphy
54
how many of the insulinomas have metastatic disease evident at surgery
50%
55
What is the medical tx of insulinomas
- dietary management
- low dose glucocorticoids
- high doses glucorticoids and diazoxides
o inhibits pancreatic insulin secretion
- streptozozin
o selectively destroys pancreatic B cells
- somatostatin analouges
- allatoin
o B cell cytotoxin
- GH, GH receptor, Insulin-like growth factor 1
o Maybe in the future
- Toceranib
o Tyrosine kinase inhibitor
o Increased survival in dogs that had it after relapse after surgery
56
3 stages of insulinoma (thin tumour staging)
- Stage I: confined to pancreas
- Stage II: lymph node metastasis
- Stage III: distant metastasis
57
What management gives the best prognosis in insulinoma
Surgery and medical management upon recurrence of clinical signs
58
What are the three mechanisms of action for paraneoplastic hypoglycaemia
- secretion of insulin or insulin-like peptides
- accelerated consumption of glucose by the tumour cells
- failure of glycogenolysis or gluconeogenesis by the liver.
59
State 4 toxins that can cause hypoglycaemia
- sulfonylurea drugs (oral glucose-lowering agents)
o stimulate insulin secretion from the pancreas, enhance tissue sensitivity to insulin, decrease basal hepatic glucose production
o chlorpropamide and glipizide
- xylitol
o stimulate insulin release from B cells
o hepatic necrosis and failure
- B blockers
o Interference with adrenergic counterregulatory mechanisms
- oleander
60
give examples of causes of inadequate glucose production
Hypoglycaemia of neonates and toy breed dogs
- Most common from inadequate substrate for glycolysis and gluconeogenesis.
- Glycogen stores are small and easily depleted.
- Hepatic enzyme system may be immature.
- Brain underdeveloped (?)
Nursing animal
- premature birth
- Debilitation of the bitch or queen at parturition
- Being the runt of the litter
- Diabetes in the bitch
Weaned puppy or kitten
- Concurrent infections
- Vaccinations
- Vigorous exercise
- GI upset
- Hypothermia
- Poor nutrition
- Extended fast
- PSS or other hepatic disease
- Sepsis
- Glycogen storage disease
- Counterregulatory hormone deficiency
61
What is the mechanism behind hypoglycaemia in liver disease
Dysfunctional glycogen storage, glycogenolytic, gluconeogenetic capabilities.
62
What is the mechanism behind hypoglycemia in septic patient
- noninsulin-mediated increased consumption
o induced by inflammatory mediators ex TNF especially in macrophage-rich tissue such as spleen, liver, lungs
o hypotension or hypoxemia may increase consumption via increases in anaerobic glycolysis
- decreased intake
- decreased hepatic function
63
what protozoa is specifically associated with hypoglycaemia and hypoglycaemia at admission is a poor prognostic indicator
canine babesiosis
64
mechanism of action for hypoglycaemia in anaphylaxis
- hypoglycaemia via multiple direct and indirect mechanisms.
o increased cellular utilization
o decreased hepatic production or mobilization of glucose
o translocation of bacteria across compromised bowel mucosa leading to sepsis.
65
Give three alternatives for owners to treat emergency hypoglycaemia at home
karo syrup, pancake syrup, or honey oral mucous membranes
66
why cant dextrose 5% in water be used as a sole fluid for tx of hypoglycmeia
can result in severe, possible life threatening hypoNa
67
how can you reduce the risk of peripheral catheter phlebitis from dextrose infusion?
- lower dextrose concentrations
- faster infusion rates of higher dextrose concentrations
- practicing elective re-siting of intravenous infusions.
68
Why should we be careful with iv dextrose in insulinoma patients
IV dextrose trigger insulin, hyperinsulinemia depress glucagon secretion – removes one of the counterregulatory mechanisms vital for maintaining euglycemia.
69
What is the mechanism for glucocorticoid in treatment of hypoglycaemia
o antagonize insulin effects and stimulate gluconeogenesis, which may help stabilize blood glucose concentration in patients with paraneoplastic or endocrine-induced hypoglycaemia, including hypoadrenocorticism and insulinoma
70
What disease should be suspected in a critical ill patient that develops hypernatremia coupled with marked polyuria in the absence of having an osmotic diuresis. 1p
* DI
71
What is diabetes insipidus? 1.5 p
* Excessive urinary electrolyte-free water (free water) loss characterized by the clinical signs of marked dilute polyuria of > 50 ml-kg-day, and obligate polydipsia to replete the excreted volume
72
What are the two types of DI? 2p
* Central DI
* Insufficient or absent arginine vasopressin
* Nephrogenic DI
* Reduced or absent receptor response to circulating AVP
73
What is the primary function of AVP and what is its main stimulus? 2 p
* Function: Homeostatic control of plasma omolality
* Main stimulus: Elevation in plasma osmolality.
* Sensed by osmoreceptors located in organum vasculosum laminae terminalis (OVLT) (rostral part of hypothalamus that lacks blood brain barrier)
74
What are stimuli of AVP release?
* Main stimulus: Elevation in plasma osmolality.
* Other:
* Hypovolemia, hypotension, a decrease of 5-10% stimulates secretion
* Stress
* Nausea
* Pain
* Certain drugs
* Hypoglycaemia
* Exercise
* Ingestion of dry food
75
What happens after the organum vasculosum laminae terminalis (OVLT) osmoreceptors have sensed elevation in plasma osmolality? 5p
* Separate osmoreceptors trigger thirst
* Circulating AVP binds Gs protein-coupled V2 receptors on the basolateral membranes of the renal collecting ducts.
* Generated a cascade of intracellular activity (adenyl cyclase activity, production of cAMP, protein kinase A activation, phosphorylation of AQP-2) eventuating in fusion of the aquaporin-2 water channel-laden cytoplasmic vesicles with the apical membrane.
* AQP-2 channels allows movement of solute-free water down its concentration gradient from the tubular lumen, through the principal cell, into the hypertonic renal medulla (via AQP3, AQP4), preventing its loss in urine
Above leads to renal absorption of water coupled with increased water intake promoted by thirst quickly brings plasma osmolality back into normal range
76
ADH triggers which type of Gprotein?
Gs
77
what are aggregophores? 1 p
- The intracytoplasmic vesicles containing aquaporin-2
78
State the actions of AVP binding to the V2 receptors? 5 p
* conservation of water
* Release of von Willebrand factor
* Release of tissue plasminogen activator
* Increased synthesis of nitric oxide (NO)
* Increased circulating concentrations of factor VIII
79
State 5 actions of AVP on V1 receptors?
* Stimulated smooth muscle contraction
* Activates PLTs
* Activates hepatic glycogenolysis and gluconeogenesis
* Adrenocorticotropic releasing hormone release from anterior pituitary
* Neurotransmitter in learning, aggression, anxiety, social behaviour
80
What diseases/conditions can cause central acquired DI? 6p
* Brain trauma
* Neoplasia
* Infectious/inflammatory
* Vascular
* Immune mediated
* Idiopathic
81
What is the most common cause of central DI in dogs? And in cats?
* Pituitary neoplasia in dogs
* Trauma in cats
82
What diseases/conditions can cause nephrogenic acquired DI? 5p
* Drugs
* Electrolyte abnormalities
* Bacterial infection
* Degenerative
* Paraneoplastic
83
Is congenital nephrogenic DI more likely to occur in females or males? And why?
* Male
* V2 receptor (AVPR2) gene linked to x chromosomes
84
What can cause reduced response to arginine vasopressin in the kidney? 1p
. Defects in V2 receptor, Abnormal AQP-2 trafficking, Abnormal AQP-2 composition
85
In people with nephorgenic DI, does apelin concetrations go up or down
apelin increases
(Hormone used as biomarker)
86
Impaired AVP synthesis, impaired axonal transport of AVP, impaired secretion of AVP by magnocellular neurons, happens with what type of DI
central DI
87
What are the risk of water deprivation test?
* Development of dullness or lethargy
* Marked hyperNa
* Marked hyperosmolality
* Azotemia
88
How can urinary clearance of free water be useful in diagnosis of DI?
* If there is a positive urinary free water clearance with concurrent hyperNa there is either central or nephrogenic DI
* Exclude all causes of PU/PD before pursuing diagnosis of cDI, nDI
89
What would be the next step to distinguish between the two?
* 1. Resolve significant hyperNa
* 2. Desmopressin trial
* Measure urine osmolality
* Empty bladder
* Administer 2-5 mcg desmopressin intranasally or as an eye drop
* Sample urine osmolality after 2-4 h. should increase by 50% or more if complete central DI or from 9-50% if partial central or nephrogenic DI. If no increase, nephrogenic DI
Why step 1?
* Desmopressin admin in central DI will lead to sudden drop in plasma Na
90
state 2 functions of the neuro-vasopeptide apelin. 2 p
* Decreases AVP release by posterior pituitary
* Interferes with AQP-2 insertion in the renal collecting tubule
-> plays a reciprocal role to AVP and increases free water excretion
91
* What medication is used in central DI and what receptor does it bind to?
* Desmopressin (DDAVP), pure V2 receptor agonist.
What other condition can above medication be used for?
* von Willebrand factor disease, type 1
92
for what conditions can desmopressin be considered
*central DI
- von Willebrand factor disease, type 1
* haemophilia A (in people, lacking evidence in dog
* Congenital PLT disorders (unpredictable effect)
* coagulopathy due to chronic uraemia improved PLT closing times in humans with uraemia and hepatic cirrhosis (unclear mechanism)
* prolonged bleeding time caused by antiplatelet drugs (aspirin, clopidogrel)
* maybe in bleeding due to colloid use
93
What is a risk with desmopressin treatment in a critically ill patient with central DI?
* Decreased plasma osmolality, hypoNa
94
Drug treatment for nephrogenic DI and the mechanism for it?
* Thiazide diuretics
* Act on Na Cl pump in distal convoluted tubule -> decreased Na absorption
* Paradoxically decreases total extracellular fluid volume, which decreases glomerular filtration rate and therefore decreases urinary output
* Tubuloglomerular feedback response mediated reduction in GFR
* Upregulatory effects on AQP 2
95
What are the risks with thiazide treatment and how do you avoid the risk?
* Profound free water loss when discontinuing the drug
* Replace the free water loss by calculating estimated free water loss in urine/hour (urine clearance of free water in ml/hour CFW)
* CFW rough estimate of the rate (ml/h) at which water will likely need to be administered to help maintain normoNa in that px.
96
What is the formula for urinary clearance of free water (CFW)?
* CFW = Vu x (1 – [([Na ]u + [K ]u ) / [Na ]p])
* Vu ml/h: Known volume of urine in known time period
* Na u : urine Na mmol/L
* K u: urine K mmol/L
* Na p = Plasma Na ummol/L
97
What are the classic changes seen in SIADH? 3p
* Hypoosmolar hypoNa in conjunction with urine hyperosmolality (> 100 mosm/L)
* Aka ADH release, increased aquaporins and increased free water in the body, hypoosmolality in the serum, hypoNa as Na diluted. Urine osmolality increased as measured per /l and there is less free water in the urine.
98
What are the diagnostic criteria for SIADH in people
Hypoosmolar hyponatremia
Euvolemia
Inappropriate concentrated urine – urine osmolality > 100 mOsm/L
Urine sodium concentration > 30 mmol/L
Hypoadrenocorticism excluded
99
What is the normal serum osmolality in dogs? And in cats? 2p
* Dogs 290-310 mOsm/kg, cats 308-335 mOsm/kg
100
Give three reasons for hypoosmolar euvolemic hyponatremia
Water ingestion, hypoadrenocorticism, SIADH
101
What are the 4 types of SIADH and which is most common in people?
* Type A upregulated secretion of ADH
* Type B elevated basal levels of ADH
* Type C reset osmostat
* Type D undetectable ADH
* Type A is most common
102
State 5 groups of reported causes of SIADH in dogs and state reported causes in dogs
- Physiological conditions
o GA
o Surgical procedure
- Neoplasia
o sarcoma
- Central nervous system disease
o Hydrocephalus
o meningitis
- Pulmonary disease
o Pneumonia
- uncertain effects of medications/drugs
o Vincristine/vinblastine
o Immune-mediated disease
- Idiopathic
- Liver disease
103
What has been reported to cause SIADH in cats?
* Secondary to liver disease
* After vinblastine therapy
104
* What is the tx for SIADH?
* Careful correction hypoNa
* Remove potential cause
- Aim for water intake to be less than water excretion until serum Na concentration has normalised
- loop diuretics (low dose furosemide )
o close monitor of hydration and electrolytes
- Demeclocycline
o Can be toxic, not reported in vet med
- Lithium
o Can be toxic, not reported in vet med
- Urea
o Increase free water clearance, not reported in vet med
- Vasopressin receptor antagonist, Vaptans
o Concerns for overly rapid resolution of hypoNa
o Not recommended in cases with severe hypoNa
* Summary: careful fluid restriction and/or fluid administration
105
Is cortisol protein bind?
Yes, 90-95% of cortisol in the plasma is bound to plasma proteins, especially cortisol-binding globulin transcortin (40% to transcortin, 50% to albumin, 5-10% is free)
106
Is aldosterone protein bound?
Aldosterone 60% bound to plasma proteins, 40% free form. Shorter half life of 20 minutes.
107
What are the functions of 11 beta-hydroxysteroid dehydrogenase type (11B-HSD2? 2 p
prevent cortisol from activating mineralocorticoid receptors.
convert cortisol to cortisone which does not avidly bind to mineralocorticoid receptors
108
state 4 factors that play essential roles in the regulation of aldosterone
- Increased K ion concentration in the extracellular fluid greatly increases aldosterone secretion.
- Increased angiotensin II concentration in the extracellular fluid also greatly increases aldosterone secretion.
- Increased Na ion concentration in the extracellular fluid very slightly decreases aldosterone secretion.
- ACTH from the anterior pituitary gland is necessary for aldosterone secretion but has little effect in controlling the rate of secretion in most physiological conditions.
109
What effect is tyrosine hydroxylase suspected to have in pheochromocytomas?
tyrosine hydroxylase converts tyrosine to dopa, leading to synthesis of more norepinephrine
Hypothesis: negative feedback of norepinephrine on tyrosine hydroxylase does not work normally in the tumour cells, or that the tumour metabolises norepinephrine so quickly that levels required for negative feedback are never reached
110
What % of dogs with pheo get cardiomyopathies
15% Card. iomyopathies: concentric or mixed ventricular hypertrophy, cardiomyocyte necrosis and degeneration on histopath.
111
What symptoms can be seen in dog with pheo
Hypertension, manifestations of hypertension (blindness from retinal detachment), weakness, collapse, lethargy, vomiting, diarrhea, polyuria, polydipsia, tachypnoea, abdominal distention, syncope, tachyarrhythmias, bradyarrhythmias, abdominal pain
112
what cardiac arryhtmias can been seen in dogs with pheo
Cardiac arrhythmias: 3rd degree AV block, second degree AV block secondary to hypertension, supraventricular tachycardia, paroxysmal tachycardia, ventricular ectopy
113
What clinical signs are seen in cats with pheo?
lethargy, vomiting, polyuria, polydipsia, aggression, and weight gain or were associated with systemic hypertension (congestive heart failure and retinal detachment).
114
What size of adrenal mass on AUS is more likely to be malignant
More than or equal to 20 mm
115
What stain can be used on biopsy samples to diagnose pheo
Stain with potassium dichromate solution: oxidizes catecholamines and produces a dark brown colour
116
What can be analysed on urine to diagnose pheo in dogs
urine normetanephrine
117
what preop tx should be considered in a dog with pheo
phenoxybenzamine – non competitive a-adrenerigc blockade. Decreased mortality from 48% to 13%
a-metylparatyrosine - Competitively inhibits tyrosine hydroxylase, interfering with catecholamines biosynthesis (tyrosine hydroxylase converts tyrosine to dopa, leading to synthesis of more norepinephrine)
correct any volume depletion
118
state two things that have been associated with shorter survival time and two with perioperative mortality in pheochromocytomas in dogs
Preop hypokalaemia or elevation in BUN along with concurrent nephrectomy associated with shorter survival times. neurologic deficits, weight loss, abdominal distention, acute haemorrhage caused by tumour rupture, adrenal gland tumours with major axis length 5 cm or larger, larger tumours with invasion of neighbouring structures, documented metastasis, and venous thrombosis.
Adrenal tumour size and acute haemorrhage predictive of periop mortality
119
What does circi stand for and what is the definition
Critical illness-related corticosteroid insufficiency. inadequate cellular corticosteroid activity for the severity of the patient’s disease
CIRCI: complex combination of alterations in production, plasma carriage, metabolism of, and tissue responsiveness to cortisol. Can be due to direct trauma, infarction or haemorrhage, or cytokine release that influence HPA axis
120
Give 4 examples of medicine that decrease cortisol production
ketoconazole, etomidate, propofol, opiates
121
state the 3 main mechanisms proposed to cause circi
decreased cortisol production
alteration of cortisol metabolism
target tissues resistance to cortisol
122
what electrolyte is macula densa sensitive to and if low will induce renine release
Chloride, Cl
123
5 dog breeds predisposed to hypoadrenocorticism
Portuguese Water Dog, Standard Poodle, Great Dane, Bearded Collie, West Highland White terrier, Wheaton terrier, Cairn Terriers, Cocker Spaniel, Rottweiler
124
5 causes of primary hypoadrenocorticism
- Immune mediated in most cases, autoantibodies against steroid synthesis enzymes found in some dogs
- Surgical adrenalectomy
- Infiltration of adrenal glands with neoplasia or infectious organisms
- Trauma
- Haemorrhage
- hypoperfusion
- iatrogenic caused by treatment with mitotane, trilostane, ketoconazole
125
5 causes of secondary hypoadrenocorticism
- iatrogenic
o steroid withdrawal after long term glucocorticoid therapy causing negative feedback on hypothalamus and pituitary -> decreased ACTH production -> adrenal atrophy
- hypothalamic and pituitary neoplasia
- immune mediated hypophysitis
- trauma
- hypophysectomy
126
what Na/K ratio could indicate hypoadrenocorticism
<28:1 (normal 27:1-40:1)
127
Radiographic findings in dog with hypoadrenocorticism?
microcardia, decreased pulmonary vessel size, small caudal vena cava, and microhepatica. Approximately 80% of dogs in Addisonian crisis had at least one of these radiographic abnormalities
128
what blood test can different primary from secondary hypoadrenocorticism
endogenous ACTH
129
what are the three major findings in a hyperaldosteronism patient
hypoK, hypertension, increased serum aldosterone
130
what are the differences between primary and secondary hyperaldosteronism
primary hyperaldosteronism:
- autonomous secretion of aldosterone from the adrenal cortex
- most common
Secondary hyperaldosteronism:
- decreased renal perfusion
- excessive renin production from the JGA due to neoplasia or decreased JGA blood flow
131
what % of hyperaldosteronism in cats is due to malignant neoplasia
63%
132
How do you definitely diagnose hyperaldosteronism
elevated plasma aldosterone concentrations or aldosterone:renin ratio. Lack of suppression of aldosterone in fludrocortisone suppression test can confirm
133
what are the survival rates after adrenalectomy due to hyperaldosteronism
70-77%
134
What are two intraop and 2 postop complications for adrenalectomy due to hyperaldosteronism
Intraop complications: haemorrhage, hypotension.
Postop complications: pancreatitis, hypoadrenocorticism, AKI
135
How is Ca stored divided between stored in bone and extracellular. How is the extracellular Ca divided
99% in bone, 1 % extracellular
Extracellular: iCa 56%, complexed 10%, protein bound 34%
136
How is iCa affected by alkalosis and acidosis
Alkalosis: iCa decreased. Lessens toxicity and clinical signs of hyperCa
Acidosis: iCa increased. Worsening clinical signs of hyperCa
137
What cell in what organ produce PTH
Chief cells in parathyroid
138
What is marked hyperMg effect on PTH
PTH secretion inhibited
139
Where in the kidney tubuli has PTH the biggest effect on Ca reabsorption
Distal convoluted tubuli, also some effect ascending thick limb of Henle
140
How is calcitriol made from the vitamin D in diet
vitamin D from the diet -> transported to liver -> hydroxylation to 25-hydroxyvitamin D (calcidiol) -> proximal tubules in kidneys -> hydroxylated by 1a-hydroxylase to 1,25-dihydroxyvitamin D3 (calcitriol)
141
what receptor does calcitriol bind to
vitamin D receptor
142
via what mechanism does calcitriol increase intestinal absorption from the intestine
induces synthesis of Ca pump and the Na-phosphate co transporter, induces brush border permeability and synthesis of calbindin, stimulates Ca transport across enterocytes (transcaltachia)
143
via inhibition of what enzyme does cacitriol inhibit its own synthesis (negative feedback)
1a hydroxylase
144
What inhibits calcitriol synthesis 4 p
Synthesis inhibited by calcitriol, hypercalcemia, FGF-23 and phosphate
145
What can be analysed in the lab if vitamin D ingestion is suspected
25-hydroxyvitamin D
146
What enzyme does PTH stimulate to increase calcitriol synthesis
1a hydroxylase
147
What cells in which organ produced calcitonin
C cells in thyroid
148
What is the major target organ of calcitonin
Bone, inhibits osteoclastic resorption
149
At what level is emergency treatment for hyperCa warranted
>1.80 mmol
150
What is the bodys normal endocrine response to hyperCa 6 p
- Decreased PTH secretion
- Increased intracellular degradation of PTH in chief cells
- Decreased PTH synthesis
- Increased calcitonin secretion
- Decreased calcitriol synthesis (direct inhibition by iCa + decreased stimulation due to decreased PTH)
151
HyperCa can cause cell death, which organs are most important clinically affected
CNS, GI tract, heart, and kidneys
152
What are the symptoms of hyperCa
PU/PD, anorexia, lethargy, weakness., vomting, prerenal azotemia, chronic renal failure. Most severe when develops rabidly, as with vitamin D intoxication or rapid infusion Ca containing fluids
153
What effect will acidosis have in hyperCa
Will magnify effect
154
Give inital, secondary, and tertiary possible treatments for hypercalcemia
Underlying cause
Initial:
Fluids 0.9% NaCl
Furosemide
Calcitonin
Secondary:
Glucocorticoids
Bisphosphonates
tertiary
Sodium bicarbonate
Mithramycin
EDTA
dialysis
155
differentials for hypercalcemia
- Transient or inconsequential
- Granulomatous
- Osteolysis
- Spurious , Nonpathological
- Hyperparathyroidism
- Vitamin D toxicity
- Addison
- Renal
- Neoplasia. most common (58%)
- Idiopathic
- Temperature
156
Via inhibition of what enzyme does phosphate inhibit calcitriol synthesis
Renal 1a-hydroxylase
157
What are the three mechanisms behind humoral hypercalcemia of malignancy
- HHM (PTHrP, IL1, TNFa, TGF)
- Metastasis of solid tumours to bone
- Haematological malignancies growing in the bone
158
State 2 breeds predisposed to primary hyperparathyroidism
Keeshound, siamese
159
3 treatments for primary hyperparathyrodism
Sx (methylene blue injection to find it).
Ultrasound-guided chemical ablation (ethanol)
Ultrasonographical guided radiofrequency heat ablation
160
2 causes of vitamin D (25-hydroxyvitamin D) intoxication
Cholecalciferol: excess dietary supplementation, toxic plants (contain glycosides of calcitriol), cholecalciferol containing rodenticides
Calcipotriene: topical ointment for psoriasis
161
Differential for hypoCa
- Hypoalbuminemia (most common)
- CKD/AKI (second most common)
- Eclampsia
- Pancreatitis /inflammation
- Undefined cause (mild hypoCa)
- Ethylene glycol (oxalic acids combine with Ca and forms Ca oxalate)
- Hypoparathyroidism
- Soft tissue trauma
- Phosphate enema
- After NaHCO3 administration
162
Breeds predisposed to primary hypoparathyrodism
miniature schnauzer, poodles, GSD, terriers predisposed
163
what is the mechanism behind reduced calcitriol in primary hypoparathyrodism
PTH low, P high (as decreased urinary losses overrides the decreased bone resorption and decreased intestinal absorption
PTH normally stimulated and P inhibits 1a-hydroxylase -> low PTH and high P -> inhibited 1a-hydroxylase -> less calcitriol
164
What symptoms does cats with preclampsia get
Rare in cats: depression, weakness, tachypnoea, mild muscle tremors
165
What is the diagnosis for a px with low Ca, high P, normal renal function and low PTH
hypoparathyrodism
166
give 5 function of phosphate
constituent of phospholipids, nucleic acids involved in mitochondrial oxidative phosphorylation. Part of ATP, 2,3-DGP, cAMP. Urinary buffer. Intermediate metabolism of protein, fat, carbohydrates, component of glycogen, stimulates glycolytic enzymes (hexokinase, phosphofructokinase). Part of NADP+. Regulates enzymes in ammonaiogeneis. Inhibits 1a-hydroxylase
167
which is the major intracellular anion
phosphate, P
168
which is the major intracellular cation
potassium, K
169
causes of hypophosphatemia
maldistribution (tx DKA, carbohydrate load, insulin administration, respiratoy alkalosis or hyperventilation, TPE, refeeding syndrome, hypothermia), increased loss (primary hyperparathyrodism, fanconis, eclampsia, proximal acting diuretics, cranial trauma and DI), decreased intake (phosphate binders, vitamin D deficiency), lab error
170
symptoms of hypophosphatemia
weakness, pain (rhabdomyolysis), vomiting, nausea, anorexia, thrombocytopathy, haemolysis, reduced 2,3-DPG, leukocyte damage, neuro signs, myocardial depression, arrythmias, bone demineralization
171
causes of hyperphosphatemia
maldistribution (tumour cell lysis, tissue trauma, haemolysis, metabolic acidosis, DKA), increased intake (phosphate enemas, vitamin D intoxication, iv phosphate), decreased excretion (AKI, CKD, uroabdomen, urethral obstruction, hypoparathyroidism, hyperthyroidism), physiological (young growing animal), lab error (lipemia, hyperproteinemia)
172
where is TSH released from
anterior pituitary
173
was does T3 and T4 stand for
triiodothyronine, thyroxine
174
name 3 hormones produced by the thyroid
triiodothyronine, thyroxine, calcitonin
175
what is iodide trapping
during formation of thyroid hormone: Iodide from absorption in GI tract is pumped via sodium-iodide pump symporter across basolateral membrane into thyroid cell. Na K Atpase pump pumps Na out of cells and established concentration gradient. Process called iodide trapping, stimulated by TSH.
176
Causes of thyroid storm 4p
Hyperthyroidism in cat, dog with thyroid carcinoma, extreme over supplementation to hypothyroid dogs, uncooked organ meat fed to dogs
177
Possibly pathogenesis for thyroid storm 4p
- high levels of circulating thyroid hormones
o same levels as in stable hyperthyroid px
- rapid, acute increase of circulating thyroid hormones
- hyperactivity of sympathetic nervous system
- increase in cellular response to thyroid hormone
178
potential precipitating events for feline thyroid storm 8 p
radioactive iodine therapy
thyroidal or parathyrodial sx
abrupt withdrawal of antithyroid medication
stress
nonthyroidal illness
administration of iodinated contrast dye
administration of stable iodine compounds
vigorous palpation of the thyroid
179
clinical signs associated with feline thyroid storm 6p
cns disturbance, hyperthermia, acute or severe V and D, abdominal pain, icterus, cardiac murmur or gallop, pleural effusion, pulmonary oedema, tachypnoea, hypertension, retinopathy, extreme muscle weakness and cervical ventroflexion, thromboembolism, sudden death
(constitutional, cardiovascular, respiratory, neuromuscular, GI and hepatic, ocular)
180
What are the diagnostic criteria for feline thyroid storm
identification of thyrotoxicosis, clinical signs, and evidence of a precipitating event
elevated total thyroxine (T4) level, or a total T4 level in the high-normal range combined with an elevated free T4 level.
181
What is the tx for feline thyroid storm
Reduce production and secretion of thyroid hormones (thiomidazole, potassium iodide, iopanic acid, dexamethasone)
Block peripheral action of thyroid hormone (B blockers, peritoneal dialysis/plasmapheresis/haemodialysis, cholestyramine
Systemic support
182
What are the hallmarks of hypothyroid crisis in dogs
Gradual onset of mental dullness
Hypothermia
Hypoventilation
Hypothyroid cardiomyopathy
Hypotension
Skin changes, non-pitting oedema
183
What are the risk factors for hypothyroid crisis in dogs
- Rottweiler
- Middle age (median 6 years, range 4-10)
- Dogs with untreated hypothyroidism
- Concurrent disease (5/7)
o Infection most common (4/7)
o Aspiration pneumonia (3/4)
o Foreign body keratoconjunctivitis, pyometra, severe bilateral otitis, pyoderma
- Glucocorticoids
- Nsaid
- Surgery
184
What % dogs with myxoedema coma given iv levothyroxine were discharged from hospital
87%
185
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flashcards
Decks in class (25)
# Cards
-
Anaesthesia and Analgesia0
-
Cardiovascular0
-
CPR0
-
Electrolyte and Acid-Base0
-
Endocrine185
-
Extracorporeal0
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Fluid therapy0
-
Haematology, Coagulation, Hemolymphatics147
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Infectious, Inflammation299
-
Intraabdominal0
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Neurology175
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Nutrition0
-
Pharmacology, Antimicrobial0
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Renal/Urinary1
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Reproductive0
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Respiratory458
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Sepsis, SIRS, MODS, Shock0
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Transfusion Medicine82
-
Trauma, Environmental, Misc0
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Ventilation, mechanical0
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Monitoring0
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Procedures0
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Dermatology42
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ophthalmology19
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Musculoskeletal15
