Dogs and Cats 20 Flashcards
1
Q
Insulin where is it produces and its function
A
- Where is it produced? -> beta cells within pancreas
- What is its function?
○ Stimulates glucose transport from blood into muscle and adipose by Glut4 transporters
○ Stimulates protein metabolism
○ Increases glycolysis in liver and activates glycogen synthase to store glucose as glycogen
○ In a fed state promotes fatty acid storage as triglycerides in adipose tissue
2
Q
Define diabetes mellitus and the cause in dogs and cats
A
- group of diseases with multiple aetiologies characterized by hyperglycaemia resulting from inadequate insulin secretion, insulin action or both.”
Aetiology - Dogs
○ Majority - insulin dependent DM - TYPE 1 DM or juvenile onset DM
○ Absolute insulin deficiency
○ Reliance of life-long exogenous insulin to survive - Cats
○ Majority - non-insulin dependent - TYPE 2 DM
○ Peripheral insulin resistance and inadequate insulin secretion
§ Due to a beta-cell dysfunction which is caused by number of factors including amyloid deposition, glucose toxicity (chronic hyperglycaemia)
□ Overtime hyperglycaemia causing insulin resistance becomes irreversible
○ Possibly reversible
3
Q
What are the 6 main predisposition and risk factors for diabetes mellitus
A
- Genetic
○ Breeds/family odds
§ Different breeds in different countries can have different predisposition - Age
○ Middle-aged to older pets - Sex
○ Not consistently reported across all studies
§ Dogs: Female>Male - in some countries females are not spayed -> hormones may affect insulin resistance
§ Cats: Male>Female - Obesity
○ Particularly in cats - nearly 4 times more likely to develop
§ Every 1kg gains insulin resistance increases by 30% - Physical inactivity
- Concurrent diseases/drugs
○ Examples
§ Pancreatitis - insulin deficiency
Prednisolone - insulin resistance (antagonist for insulin)
4
Q
What are the main clinical signs of diabetes mellitus
A
1) PUPD
2) polyphagia
3) muscle loss, poor tissue regeneration and function
Additional clinical signs
4) Eye changes in dogs
○ 3/4 cataract within first year of diagnosis - in DOGS
§ Initially glucose in lens metabolised into sorbitol (cannot leave the eye, increase production, brings in water -> eye swells -> cataracts)
5) Plantigrade stance in cats (diabetic neuropathy)
6) +Exercise intolerance
7) +Recurrent infections
8) +signs of diabetic ketoacidosis
○ E.g. ketotic breath
5
Q
what is the renal threshold for dogs and cats
A
Renal threshold - glucose in urine -> osmotic diuresis -> PU/PD
- Dog 12mmol/L
- Cat 15-16mmol/L
6
Q
Diagnosis for diabetes mellitus what are the 5 main ones
A
- Persistent fasting hyperglycaemia and glucosuria in a pet displaying appropriate clinical signs
- Haematology - may see stress hyperglycaemia or concurrent infection
- Biochemistry - hypercholesterinaemia, ALP, ALT increase
Top 2 - more for secondary conditions that complicate treatment - hypothyroidism, pancreatitis, urinary tract infection - Urinalysis - apart from glucosuria, other findings include proteinuria, ketonuria (DKA) and signs of UTI on sediment
- Imaging - change in pancreases for ultrasound if pancreatitis, enlarged liver on radiograph
7
Q
How to differentiate persistent fasting hyperglycaemia and glucosuria from diabetes mellitus from stress hyperglycaemia
A
○ What about stress hyperglycaemia? - common in cats
§ Are there clinical signs -> if YES then likely diabetes (shouldn’t have clinical signs in stress hyperglycaemia)
§ Re-measure urine/blood glucose at home +/-
□ 3 days after so stress is reduced
§ Fructosamine test -> if elevated then too much sugar in blood for previous 2 weeks
8
Q
Dogs presenting with PUPD what are common and uncommon causes
A
- Common
○ Drug induced
§ E.g. Phenobarbitone, Prednisolone
○ Hyperadrenocorticism - cushings disease - Uncommon
○ SARDS - generally present with blindness
○ Acromegaly
○ Hepatic encephalopathy - PSS
§ Generally not associated with polyphagia however toxins may affect brain leading to this
9
Q
Cays presenting with PUPD what are common and uncommon causes
A
- Common ○ Hyperthyroidism - Less common ○ Acromegaly ○ Drug induced ○ Hepatopathy - Rare ○ Hyperadrenocorticism
10
Q
What are the differentials for hyperglycaemia and glucosuria
A
Hyperglycaemia - DDX: ○ Drugs ○ Disorders associated with insulin antagonism ○ Stress Glucosuria - DDX: ○ Renal tubular disease ○ Laboratory interference - high amount of Vitamin C leads to discolouration of dipstick ○ Stress
11
Q
What are the goals in the treatment of diabetes mellitus
A
- Owner perceived good QOL and satisfaction with treatment
○ Resolution of clinical signs
§ Glucose concentration below renal threshold
○ Optimisation of weight, activity level and body condition
○ Remission if possible in cats
§ Tight glycaemic control
○ Prevent/minimize complications, including hypoglycaemia
12
Q
what are the 4 components in treating diabetes mellitus
A
1) diet
2) insulin - management
3) address concurrent disease
4) weight loss via exercise - support weight loss, should be constant
13
Q
Diet management for diabetes mellitus treatment how do and what important for
A
○ Constant between days! - large effect on glucose concentration
§ Same calories
§ Same volume
§ Same composition
§ Same feeding frequency
○ Important for weight loss as well
§ Dogs: Adjust fibre content depending on bodyweight
□ Can feed dogs morning and night
§ Cats: Restrict carbohydrate content - important prognostic factor in cat
14
Q
Insulin management to treat diabetes mellitus how to get started on a program
A
§ Create a realistic treatment protocol FOR THE PATIENT AND OWNER
□ This is an important factor that may lead to euthanasia
§ Start with insulin q 12 +2 hrs* together with regular diet
§ Set up monitoring plan
§ Inform of monitoring for and management of hypoglycaemia
15
Q
What are the types of insulin to use for diabetes mellitus and most common in dogs and cats
A
Types - glargine, PZI, porcine lente, NPH, regular insulin
- Mainstay of DM treatment
- Different insulins have
- Different longevity
- Different potency
- Ability to cause antibodies
Most common
- dogs - caninsulin, a porcine lente insuin
- cats - lantus, a synthetic insulin analogue
16
Q
Starting insulin treatment for diabetes mellitus what dose at what frequency for what BG and specific to cats
A
§ Instructions □ Intermediate or long-lasting insulin (rounded down to nearest full IU) ® 0.25 IU/kg q 12 hrsif BG < 20 mmol/L ® 0.5 IU/kg q 12 hrsif BG >20 mmol/L □ Dose according to ideal BW □ Specific to cats: ® Do not give > 3 IU/cat initially ® Do not give > 1 IU/cat q 12 hrs if no blood monitoring is performed in first week
17
Q
Monitoring insulin treatment in a diabetic frequency and what is essential at each visit
A
§ Frequency
□ Recommended
® Weekly (+2 days) in first month or after dose increases
® Then monthly for 2 months
® Every 3-4 months when stable
§ Can be more frequent in cases of hypoglycaemia
§ Essential at each visit
□ Information from home: Home monitoring diary or log
® How much eat and drink any activity, issues or adverse effects
18
Q
Insulin monitoring during diabetes mellitus treatment what are traditional tests
A
1) Urine –dipstick for glucose and ketones
2) Blood glucose curves
® Usually every 2 hrs for 12 hours
® May be done at home or in hospital
® Home glucose sampling video
3) Fructosamine
® Proteins within the blood have glucose bound to them, stay within the blood until metabolised which takes 1-2 weeks
◊ Hyperthyroidism - increase protein metabolism so can change the results
® - is not affected by stress
® Disadvantage - average out - may not be able to pick up hypoglycaemia and hyperglycaemia
® Different reference ranges based on laboratory
19
Q
What are the new systems for monitoring insulin in diabetic patients
A
§ New systems - measure tissue glucose NOT blood glucose - detects and sends information to detector every minute
□ Not painful so can go home with, not as much affected from stress as well
□ Types
® Continuous glucose monitoring
® Fresh glucose monitor
20
Q
Glucose curve what are the 4 things you want to identify and what use it for
A
□ What is the glucose concentration before insulin is given
□ What is the nadir - lowest glucose concentration for duration of insulin effect
□ Duration of insulin action -> how long under the renal threshold
□ Duration above the target glucose range -> how long above renal threshold -> when we expect contribution to clinical signs
- Then use the glucose curve to determine whether need change dose of treatment based on recommendations
21
Q
In monitoring for diabetes mellitus what monitoring for and management
A
□ Signs
® Changes in demeanour:
◊ E.g. Irritability, aggression, aimless wandering
® Hunger, seeking food
® If no treatment -> Ataxia, seizures, coma, death
□ Management:
® Act quickly!
® If pet is conscious offer food
® If pet is unable to eat apply glucose syrup or honey to oral membranes
® If pet is obtunded give glucose IV
◊ Glucagon CRIs may be used in severe cases of insulin overdose
® Don’t forget to reduce the next insulin doses -> reduce insulin by 50%
22
Q
In terms of treating diabetes mellitus what is involved in addressing concurrent diseases
A
○ Concurrent diseases may lead to an inability to stabilize the diabetes mellitus quickly.
○ Address infections if present
○ Perform dental treatment as soon as possible if necessary
○ Spay female entire dogs as soon as possible
§ Progesterone insulin antagonist and mammary gland producing growth hormone (another insulin antagonist) - HIGH in dioestrus or pregnancy - CAN TIP OVER THE EDGE
○ Discontinue any diabetogenic drugs if possible
23
Q
Which species can achieve remission from diabetes mellitus, define and which are more likely to achieve
A
- Definition: Euglycaemia without insulin therapy or hypoglycaemic drugs for > 2 weeks
- Cats are more likely to achieve remission if
○ Medication that antagonizes insulin (e.g. prednisolone) was present in last 6 months and has been discontinued
○ Excellent glycaemic control is achieved in < 6 months from diagnosis
○ Required insulin dose to achieve tight control is low
24
Q
Diabetes mellitus remission in cats best achieved with and what is important to remember
A
- Best achieved with:
○ Long-acting insulins
○ Low carbohydrate, high protein diets
○ Rapid initiation of therapy (early diagnosis)
○ Intensive monitoring of blood/tissue glucose and appropriate insulin adjustment - Remission may not be permanent
○ Cats should be maintained on low carbohydrate diet
○ Regular monitoring for DM advised
25
Prognosis of diabetes mellitus what does it depend on, dogs and cats MST
```
- Depends on
○ Owner commitment
○ Presence of concurrent disorders
- Dogs - generally older and have concurrent conditions - may be euthanised due to lack of ability to monitor
○ MST 2-3 years
- Cats
○ MST 1-2.5 years
- If pets are stabilized well many live longer then MST
```
26
How to recognise an unstable or complicated diabetic
- Signs of diabetes mellitus do not resolve or recur - PU/PD should resolve within 2 weeks
- Signs suggestive of sequelae occur - Persistent hypoglycaemia, infections,
- Laboratory parameters suggest poor control
- Insulin doses needed to achieve control are > 2.2 iu/kg (most animals 0.5iu/kg maintained on, can be up to 1)
- Insulin requirements change often
27
What are common consequences of poor diabetes control in a dog
- affect the quality of life - may result in euthanasia
Dogs
- Cataracts, blindness and anterior uveitis
- Chronic pancreatitis
- Recurrent infections
- Hypoglycaemia
- Ketoacidosis
28
What are common consequences of poor diabetes control in a cat
affect the quality of life - may result in euthanasia
- Peripheral neuropathy
- Weight loss and poor grooming
- Hypoglycaemia
- Recurrent ketosis or DKA
- Hyperglycaemic hyperosmolar syndrome - rare but can be life threatening
○ Low enough that not getting acidosis but high enough getting this osmolarity
○ increase osmolarity in blood which draws water from cells -> intracellular hypotonicity (shrinking of cells -> mainly neurological cells) resulting in neurological signs
29
What are the 5 steps in approaching the unstable diabetic
1. Rule out management errors - large proportional of issues
2. Discontinue any diabetogenic drugs - glucocorticoids, progestagens, phenylpropanolamine
3. Rule out insulin problems
4. Increase the insulin dose ever 5-7 days until 1-1.5 iu/kg lean BW twice daily is achieved
5. Perform a blood glucose curve, Fructosamine +/- other tests to assess
○ Insulin resistance, inappropriate length of insulin action, overdosing
30
In terms of approaching a unstable diabetic how to rule out management errors
○ What syringes are used?
○ How is the insulin drawn up?
○ How is the insulin injected? -> skin tent -> need to rotate areas being injected to prevent fibrosis formation
○ What diet and exercise regime is used?
31
In terms of approaching a unstable diabetic how to rule out insulin problems
○ Storage
○ Mixing - role gently between the hands - DON'T SHAKE (crystals could accumulate at bottom, microbubbles formation)
○ Diluting - not recommended, glargine CANNOT BE DILUTED - change pH may precipitate in bottle not body - ineffective
○ Discolouration - suggests contamination or out of date
○ Date of expiry - can be used longer if proper storage - main issue is contamination but can be effective above this
32
Why not just a spot glucose
For cost reasons
- Spot glucose when see the animal and that is it
- Good to identify hypoglycaemia to decrease insulin
- NOT GOOD for identifying issues with diabetic control and adjusting insulin upwards
33
In a complicated diabetic case what can a high dructoasmine concentration may indicate
§ Insulin resistance, insulin underdoing and insulin overdosing
□ Insulin overdosing -> can cause hyperglycaemia that lasts days - as Fructosamine
§ WHY NEED BLOOD GLUCOSE CURVE
34
Insulin resistance why may occur and what hormones act as insulin antagnoists
- May occur because there are problems
○ Before insulin binds at its receptor -> if cannot bind or no receptors to bind to - GLUT4 transporter
○ During binding to the receptor, or
○ During post-receptor interaction
- There are several hormones that act as insulin antagonists
○ Progesterone, cortisol, glucagon, adrenalin and noradrenalin, growth hormone
35
Acromegaly what is it, causes and clinical features
- A disorder in which the pituitary gland produces too much growth hormone.
Causes of severe insulin resistance in both species, but different aetiology
Clinical features
- Respiratory stridor
- Dental spacing - growth in the mouth
- Prognathia inferior -> jaw protruding cranial mandibular
- Broad facial features
- Lameness
- Clubbed feet
- Organomegaly
- Neurological signs (cats) - due to the pituitary growth
36
Acromegaly diagnosis
```
- Suspicion:
○ Clinical signs or
○ Weight gain despite poor control of DM
○ Female entire dog with DM
- IGF-1 Measurement
- GH measurement if available
- CT or MRI in cats - specialist
```
37
Phaeochromocytoma what is it, how common, general age and clinical signs
- Catecholamine producing tumour
- Uncommon in dogs and rare in cats
- Most patients are older (median 11 years)
Clinical signs
- Related to effect of catecholamines
○ Hypertension
○ Weakness and collapse
○ Tachycardia
○ PUPD
- Related to invasion of other organs
- In some cases no signs!
38
Phaeochromocytoma differentials and diagnosis
```
Differential for adrenal masses
1. Hormone secretion (functional)
○ Hyperadrenocorticism (dogs)
○ Sex-hormone secreting mass
○ Phaechromocytoma
○ Hyperaldosteronism (cats)
2. Non-functional
○ Adenomas, carcinomas, metastasis
Diagnosis
- Haematology, serum biochemistry and urinalysis
- Blood pressure measurement
- Funduscopic examination
- Diagnostic imaging
- Plasma and urine catecholamine measurements
```
39
Phaeochromocytoma treatment and prognosis
- Phenoxybenzamine
- Surgery
- Prognosis is guarded-good if the tumour can be excised.
○ >1-2 years survival
40
Glucagonoma how common, tumour in, clinical features, diagnosis, treatment and prognosis
- Rare
- Tumour in
○ pancreas (D)
○ Liver (C)
- Main clinical features are
○ Necrolytic migratory erythema
○ Uncontrolled diabetes mellitus
- Diagnosis requires advanced testing
- Treatment is surgical
○ Medical treatment may play a role in future
- Prognosis is poor; metastasis at the time of diagnosis is common
41
What is Diabetic ketoacidosis (DKA)
- A complication of diabetes mellitus that is associate with ketoacidosis
Ø Life-threatening
Ø Requires emergency treatment
- Its common
42
Counter-regulatory hormones in DKA and what are some catabolic or stress hormones
- Concurrent disease -> increases counter-regulatory hormones and insulin resistance (increased in times of stress/disease)
- Catabolic or stress hormones
○ Glucagon
○ Growth hormone
○ Adrenaline
○ Cortisol
43
Pathophysiology of DKA what occurs and why
Glycolysis stimulated by insulin -> makes TCA cycle go FASTER
Lipolysis stimulated by glucagon -> TCA cycle goes SLOWER
Not enough insulin or insulin resistant
- Less glycolysis -> less drive of TCA cycle (within starvation state -> glucagon dominance to produce energy) -> build-up of acetyl Co A -> drives production of ketones (so can use as energy) -> EXCESSIVE KETONE PRODUCTION -> body cannot handle
44
What are the 3 main things that excess ketones cause
sick and dehydrated patient
1. Anorexia and vomiting -> chemoreceptor trigger zone
2. Diuresis -> over and above glucose -> DOUBLE (both ketone and glucose)
3. Acidosis -> overwhelm body acid-base balance
Lead to the downward spiral that lead to death in DKA patients
45
What is common presentation for a DKA case
- recent stress - such as history
- previous diabetic with no insulin for 2 days - MOST DKA HAVEN'T BEEN DIAGNOSED AS A DIABETIC
- vomiting - SICK DIABETIC
46
Diagnosis of DKA
- clinical signs/presentation
- Sick (or stressed) patient
○ Hyperglycaemia
○ Metabolic acidosis (High AG without high lactate) - SBE negative
- Ketones -Detecting ketones
□ Blood and urine
- glucose increase - glucosuria
- AG -> anion gap is HIGH -> DUE TO KETONES
-> If this is high and lactate NOT -> likely due to ketones
47
What are the 4 main components of treatment for DKA
1) fluid therapy
2) correction of electrolyte and acid base derangements
3) regular insulin
4) treatment of concurrent disease - always look for concurrent disease
48
Fluid therapy for DKA patient
○ Correct hypovolaemia first, deficit, maintenance, losses (INCREASED DUE TO DIERUSIS)
§ Bolus to increase pulse, hartmann's
§ Also acts to dilute out ketones and hyperglycaemia and flush them out
□ As glucose drops here
49
Correction of electrolyte and acid base derangement for DKA treatment
1. Low Na+ -> as glucose acting as osmoles and bringing water into vascular space dilutes Na+
§ So actual number of Na+ probably normal or increased
□ (2 x Na+) + glucose = osmolarity
2. K+ will fall with insulin therapy and fluid therapy - MONITOR
□ Insulin shifts potassium into cells
3. Phosphate supplementation
® Totally body P - often depleted - as diluted same as Na+
® Supplement phosphate if <1mmol/L
◊ Rule of thumb: give half of the supplemented potassium as KPO4
® Normally for K give KCl but not in this case
4. Magnesium - ionised Mg may be low in cats
§ Always measure Mg before supplementing as easy to cause toxicity
5. Use bicarbonate - RARELY INDICATED FOR DKA
® Helps to partially correct the metabolic acidosis
® Risks
◊ Worsening of hypokalaemia, impaired ketone metabolism, hypernatraemia, hyperosmolality
50
Regular insulin in treatment of DKA what does it do, 2 main ways and monitoring
○ Insulin to increase TCA cycle and reduce the acetyl Co A and ketones
○ Procedures -> both same outcome
® CRI
□ Rapid onset, required a fluid pump, 24-hour care BEST
® IM
□ Less intensive monitoring
□ Delayed onset of action
□ Longer half-life
□ Less comfortable for patient
○ Monitoring glucose via catheter or hypodermic needle on pinna (to get a drop of blood)
® Insulin CRI - q 2-4h
® IM insulin - q 4-6h
® Continuous glucose monitors
◊ Require patient to be hydrated -> reading subcutaneous glucose - not useful for first 24-48 hours of DKA management
51
Treatment of concurrent disease for DKA patient what are common and treatments
```
○ The concurrent disease has increased counter-regulatory mechanisms - NEED TO FIX TO FIX DKA
○ Common
® Pancreatitis
® Pyometra
® UTI
® Hyperadrenocorticism
○ Treatments
® Opioids
® Antibiotics
® Anti-emetics
```
52
DKA patient what to tell patient and prognosis
```
What to tell the owners
- All patients require hospitalisation
- 24 hour critical care is best
- 70% will spend > 5 days in hospital
○ 4-5 thousand in hospitals
Prognosis
- Most (70%) dogs and cats survive to discharge
- Five days in hospital
- 7% of dogs and up to 40% of cats have recurrent episodes of DKA
```
53
what is cortisol and its regulation
Cortisol
- Stress hormone produced by the zona fasciculata and zona reticularis of cortex of adrenal gland
Regulation
- ACTH released from pituitary gland stimulates the release of cortisol from the adrenal glands
- In return, cortisol production causes reduction of release of ACTH from the pituitary (negative feedback)
54
Hypoadrenocorticism how common, what does it reflect and clinical signs
- Uncommon disease, most common in young adult dogs, rarely cats
- Disease reflects deficiency of glucocorticoids +/- mineralocorticoids
- Vague clinical signs: lethargy, weight loss, weakness, vomiting, diarrhoea
55
Hypoadrenocorticism what is the main form/cause and what is impaired
Primary adrenal hypoadrenocorticism (AKA Addison’s disease)
- Due to destruction of the adrenal cortices
○ Most commonly idiopathic immune-mediated destruction
○ May also be induced by adrenal toxicity, adrenalitis, or haemorrhage/necrosis
- Most common cause in small animals
- Requires severe bilateral loss of cortical tissue (>90% cortical loss)
- Both mineralocorticoid and glucocorticoid secretion impaired
56
Hypoadrenocorticism what are the 2 other causes/forms
2. Secondary/pituitary-dependent hypoadrenocorticism - MOST COMMON IN DOGS
- Due to inadequate ACTH secretion by the pituitary (eg. destruction by inflammation or neoplasia)
- Glucocorticoids deficiency only, mineralocorticoid secretion unaffected
3. Iatrogenic hypoadrenocorticism
- Temporary hypoadrenocorticism following sudden discontinuation of corticosteroid therapy
○ Glucocorticoid deficiency until signalling pathway stimulates the adrenals to start producing corticosteroids again
57
Hypoadrenocorticism what are the main effects
- Mineralocorticoid deficiency causes hypovolaemia (which may lead to hypovolaemic shock in severe cases), hyperkalaemia, hyponatraemia, hypochloridaemia and metabolic acidosis.
- Glucocorticoid deficiency results in poor stress tolerance and suppresses gluconeogenesis, leading to mild hypoglycemia
- Rarely also develop alopecia or hyperpigmentation
58
Hypoadrenocorticism signalment
```
○ Disease of middle-aged to old dogs
○ Sex
○ PDH: Male = Female
○ AT: Male < Female
○ Common in certain breeds -> Poodles, terriers, dachshunds
```
59
Hypoadrenocorticism clinical signs and why occurs
○ PUPD - present in almost all cases and is often the presenting complaint
§ May be apparent weeks to months earlier than other signs
○ Polyphagia - assumed to be directly related to excess cortisol release
○ Pot-belly - abdominal distention
§ Present in most cases due to muscle weakness, fat redistribution and/or hepatomegaly
○ Lethargy
○ Muscle weakness and atrophy - generally prominent of the region of the spine, the temporal muscles and the thigh region
§ Generally gradual so not presented with, thought to be age-related
§ Inability to go for longer walks, climb stairs
○ Other
§ Respiratory signs - panting and shortness of breath - could be due to muscle weakness
§ Neurological signs - can have pituitary macroadenomas that have neurological signs
□ Blindness, aimless wandering, circling, behavioural changes, seizures
§ Anoestrus and clitoral enlargement
§ Hypotension - may be seen in untreated dogs -> proteinuria -> deterioration of kidney function
§ Dermatological changes - more prominent blood vessels, increase bruising, alopecia non-puritic, calanosis cutosis
60
Hypoadrenocorticism in terms of clinicalpathology what ruling out and main findings in haemtology, biochem and urinalysis
○ Rule out other concurrent conditions - diabetes
○ Haematology
§ Leukocytosis
§ Stress leukogram
§ +Thrombocytosis
§ +Erythrocytosis
○ Serum biochemistry
§ ALP elevation -> steroid isoform of ALP in dogs -> NOT IN CATS
§ ALT elevation -> metabolization of fat or protein, hepatic lipidosis -> but a smaller increase than ALP
§ Hypercholesterolaemia
§ +Hyperglycaemia
§ +low urea
○ Urinalysis
§ SG 1.008-1.012, or below - 80% HAVE THIS
§ Signs of urinary tract bacteria (‘active sediment’)
§ +Proteinuria
61
Hypoadrenocorticism imaging findings
○ Abdominal radiographs
○ Abdominal ultrasonography -> really good
○ Pituitary imaging
○ Abdominal CT
62
Hypoadrenocorticism what 2 diseases does it effect the diagnosis of
- Diagnosis of hypothyroidism becomes difficult
○ Reduction in circulating T4/T3/fT4/TSH concentration possible
○ Can make it impossible to diagnose -> may need to treat for HAC and then identify hypothyroidism
- Diagnosis of HAC is more difficult in DM dogs
○ Stress of DM can influence endocrine tests -> we are testing stress response in endocrine testing - MAY FALSELY DIAGNOSE
○ Try to stabilise DM first and get on top of infections
○ (HAC results in increased insulin secretion)
63
Hypoadrenocorticism tests to identify and then identify and differentiate list 3
```
Test to identify
1) ACTH stimulation tests
2) 17-OH progesterone test
3) urine cortisol:creatinine ratio
Test to identify and differentiate
1) low dose dexamethasone suppression test
2) high dose dexamethasone suppression test
3) ACTH assay
```
64
ACTH stimulation test how to perform and interpretation
How to occur
§ Take blood sample - measure basal cortisol level
§ Give synthetic ACTH that stimulate adrenal gland and test the reserve
§ 1 hour later take second blood sample and use information to diagnose
Interpretation
Normal - increase to 50-400nmol/L
PDH or AT - larger adrenal glands - exaggerated response - above 550nmol/L diagnostic
- Grey zone -> could be decrease response or stress 450-550nmol/L
○ Therefore not recommended in concurrent disease as may lead to stress
HypoA or Iatrogenic - <50nmol/L
DIFFERENTIATE BETWEEN EXOGENOUS OR ENDOGENOUS USE
65
Low dose dexamethasone suppression test how to perform, what occurs and interpretation with sentivity vs specificity
§ Base line cortisol blood levels
§ Give dexamethasone -> negative feedback on pituitary - suppression of adrenal gland production of cortisol
Interpretation
- After 3 hours should be suppressed and maintained over 8 hours
Very sensitive -> so if normal DOESN'T HAVE
1. no suppression - adrenal tumour or pituitary disease
2. suppress into normal reference range within 3 hours but then escape -> pituitary dependent
3. suppress at 3 an 8 hours but not low enough (more than 50% of baseline value but not into normal range) - pituitary
4. stay high at 3 and then suppress at 8 hours - pituitary dependent
SPECIFICITY CAN BE LOW THOUGH
66
Treatment overview for Pituitary dependent Hypoadrenocorticism and adrenal tumour
1) Trilostane - most common
- mitotane, hypophysectomy
2) AT - adrenalectomy - surgery - CURATIVE
- Never treat a dog without unambiguous clinical signs - EVEN WITH CLINICALPATHOLOGICAL CHANGES
- There are other treatments – not recommended
67
Trilostane for Pituitary dependent Hypoadrenocorticism treatment what is it, dosing and adverse effects
```
§ Competitive inhibitor of enzyme in cortisol production pathway
§ Twice daily dosing recommended -> split dose overtime help decrease the risk of adverse effects
§ Adverse effects are not uncommon
□ GI adverse effects
□ Hyperkalaemia
□ Hypoadrenocorticism
□ Adrenal necrosis
□ Nelson’s phenomenon
```
68
Trilostane monitoring traditional how done, what needs to be monitored and how to perform for Hypoadrenocorticism
via ACTH ST
□ Owner to monitor clinical signs
® Important for adjustment - ADJUSTMENT NEEDED AS CERTAIN DOSES REDUCE SIGNS OF CUSHINGS DISEASE AND RISK OF ADVERSE EFFECTS
® Should take 2-4 weeks for PU/PD to resolve
□ Perform an ACTH stimulation test
® Recommended to start 2 hours post pill –peak effect - ENSURE OWNER GIVES TABLET
◊ Pre-pill ACTH ST done in some cases to assess duration of trilostane effect
® Key values of post ACTH cortisol: - KNOW THIS
◊ <40 nmol/L: suggestive of hypocortisolaemia - risk of addisions disease
>150nmol/L: suggestive of hypercortisolaemia - risk of getting clinical signs
69
What are the 3 main options with changing trilostane based on what for Hypoadrenocorticism
1) signs of hypocortisolaemia or cortisol withdrawal
2) normal appetite, no PUPD, normal on check up
3) increased appetite PUPD, panting at check up
Then based on post ACTH cortisol
70
How to monitor trilostane for Hypoadrenocorticism treatment without using ACTH ST why would you do this and how
□ Why?
® ACTH is expensive and not always available
□ How?
® Owner to report the clinical signs
® Measure the pre-pill cortisol concentration
◊ In some cases the 3 hour post-pill cortisol concentration may be useful
® Use a validated owner questionnaire (see LMS
◊ Unwell: >3 PI or score <4
◊ Excellent control: score 4-11
◊ Reasonable control: score 12-16
◊ Poor control: score >17
71
What is the prognosis for PDH (pituitary dependent hypoadrenocorticism) and AT
- PDH
○ Control within 3-6 months of trilostane
- AT
○ Median survival of 353d with trilostane BUT 2-4 years with surgery
○ Prognostic factors for surgery -> larger tumour >5cm, vein thombosis and metastasis worse
72
What is osmolality, tonicity and why important
- Osmolality - concentration of osmoles within a system - NOT NUMBER OF PARTICLES
- Tonicity - when comparing two compartments on their osmolality -> hypertonic
○ Osmotic pressure gradients
- Ideal intracellular osmolality is important for cell function
○ Water shifts quickly
○ Particles shift slowly
○ Free water loss can lead to dramatic increases in ICS osmolality
§ In response -> Produce idiogenic osmoles -> act as osmotic force to ensure water remains within the cells
73
Why is osmolality important in animals with marked PUPD
- If animals are prevented from drinking, life-threatening intracellular dehydration can develop
- If animals have been dehydrated for a period >24 hrs, and are quickly re-hydrated, life-threatening intracellular oedema can develop (system most effected is the brain)
- RAPID OSMOLALITY CHANGES SHOULD BE AVOIDED (maximum 12 mmol/L per 24 hrsof sodium-change as a guide)
74
How to calculate osmolality and what is found in patients with PU and PD
- 2(Na+K) + urea + glucose= Calculated osmolality ECF
- Calculated osmolality is
○ Normal to high in patients with primary PU -> increase concentration of osmoses as LOSING MORE WATER
○ Normal to low in patients with primary PD -> decrease concentration of osmoses as GAINING MORE WATER
75
ADH hormone production, secretion and action
- Production: Hypothalamus
- Secretion: Pituitary
- Action: Tubular cells of kidneys
○ Binding to V2 Receptors
○ Aquaporin channels are introduced into membranes of distal tubule
- Net effect: free water absorption -> HYDRATION
76
Primary (psychogenic) polydipsia how common, what occurs and what often assocaited with
- Uncommon condition
- Excessive (unnecessary) water intake
○ Alteration in thirst centre
○ Alteration in osmoregulation
○ Faulty hormonal or neuronal stimuli
- Often associated with behavioural problems
77
Syndrome of inappropriate ADH secretion (SIADH) how common, what occurs and aim of diagnostic
- Extremely rare
- Inappropriate secretion of ADH
○ Plasma osmolality reduces
○ Dogs (cat) present with neurological signs
○ Marked hyponatraemia is present
- Diagnostic work up aims to rule out other causes of hyponatraemia
78
Diabetes insipidus what is it, results in
- Diabetes insipidus reflects a fault in ADH production, secretion or action
- RESULTING in decrease water absorption
- Results in severe PU and subsequent PD
○ Water intake often 5-20x normal
○ Urine SG often markedly hyposthenuric
79
What are the 2 main types of diabetes insipidus, how common, what occurs and causes
1. Central diabetes insipidus
- Lack of ADH production or secretion
- Primary CDI is uncommon!
- Causes
○ Neoplasia (especially dogs)
○ Trauma (especially cats)
○ Infection
○ Developmental diseases
○ Idiopathic
2. Nephrogenic diabetes insipidus
- Lack of ADH action at renal tubular cells
- Primary NDH is rare!
○ Juvenile NDH in Siberian Huskies
§ Lack of V2 receptors
80
What are the primary, secondary and tertiary tests for diagnostic approach to case with marked PUPD and what rule out
```
1. Primary tests
○ Urinalysis
○ Urine culture
○ CBC biochemistry
2. Secondary
○ Liver function test
○ Abdominal ultrasound
○ Endocrine tests
RULE OUT OTHER DISEASES AT THIS POINT - hyperadrenocorticism, diabetes, renal disease
3. Tertiary tests - diagnosis of diabetes insipidus
a. Brain imaging (CT/MRI)
b. Modified water deprivation test
c. Trial therapy with DDAVP
TALK TO SPECIALIST BEFORE PERFORMING ANY TESTS
```
81
The modified water deprivation test what used for, and what is important to consider
Patietn with marked PUPD
- This test can be life-threatening - can cause dramatic shifts of fluids in the body
- It requires constant monitoring
- Before considering this test, consult with a specialist about your patient
82
Desmopressin Trial Therapy what used for, what does it identify and advantages and disadvantages
- PUPD should resolve completely if CDI - replaces the
- Advantages
○ Less life-threatening
○ Can be done at home
- Disadvantages
○ No reliable differentiation between primary and secondary disease
○ Water toxicosis in PPD dogs (primary PU dogs)
83
Prognosis for Diabetes insipidus and the different types
- Depends on the underlying disease
- Idiopathic CDI can often be adequately controlled
- Primary NDI is much harder to control, and ineffective in some cases
○ Prognosis is guarded to poor
- Needs to be studied further in PPD dogs
84
What are the 3 main causes of PUPD but otherwise well
- Diabetes mellitus (early/stable)
- Hyperadrenocorticism (skin/coat)
- Primary polydipsia
85
What are the main causes of PUPD and are often clinically unwell
- Renal disease
- Pyelonephritis
- Pyometra
- Hypoadrenocorticism
- Hyperthyroidism
- DKA/Hyperosmolar
- Diabetes insipidus
- Liver disease
- Hypercalcaemia
- Polycythaemia
- Hypokalaemia
- Hyperglobulinaemia
86
Calcium regulation what are the 3 main hormones involved and what do they do
1) Vitamin D - increase ca in bloodstream
§ PTH activates Vit D,
§ Increase absorption of ca in the GI tract and kidney
2) PTH - parathyroid hormone - suppressed with high calcium in blood
§ Promotes higher calcium level in bloodstream via
□ Promoting vitamin D formation in kidney
□ Increasing osteolysis in the bone
□ Promotes reabsorption of Ca from urine
3) Calcitonin - DECREASE Ca level in bloodstream
§ Promotes uptake of Ca and P in bone
§ Decrease absorption in the GIT
87
what are the fraction of calcium in the body and what is the total calcium measured
```
○ Bones: majority of calcium
○ In blood 3 fractions: - TOTAL CALCIUM
§ Ionised: 50% - metabolically active
§ Protein-bound: 40%
§ Chelated: 10%
```
88
Hypercalcaemia main signs and causes
```
- Signs - SICK PUPD
○ PUPD
○ Muscle weakness
○ GIT signs
○ Cardiac arrhythmias
○ Seizures
- Causes of hypercalcaemia
○ Hyperparathyroidism
○ Addison’s disease
○ Renal disease
○ D-Hypervitaminosis
○ Infectious or idiopathic
○ Osteolysis
○ Neoplastic
○ Spurious - laboratory error
```
89
Hypercalcaemia what are the 6 steps in the diagnostic approach and which needs a specialist and what causes looking for with each
1) Rule out spurious result
§ Fasting sample, ionised calcium
2) History - toxins?
3) Physical exam -> looking for neoplasia - lymphoma and anal gland adenocarcinoma
§ Lymphadenomegaly?
§ Anal gland enlargement
§ Other signs
4) Assess phosphorus and calcium, other bloods, urinalysis, imaging
§ Addisions disease
§ Renal failure
§ Bone lysis
§ Infection
5) PTH and PTHrp measurement - SPECIALIST
§ Neoplasia or hyperparathyroidism
□ Elevation of PTH suggests hyperparathyroidism
□ PTHrp elevation suggests neoplasia -> produced by these tumours
6) +/- vit D measurement
§ Hypervitaminosis
90
Primary hyperparathyroidism what results in, signalment and diagnosis
- Single adenoma affecting a gland secreting increased PTH -> most common
- Middle-aged to older dogs and cats
- In dogs:
○ Keeshonds predisposed
○ Often singular parathyroid adenoma
Diagnosis
- Marked hypercalcaemia
- Hypophosphataemia
- Ultrasound -> Parathyroid nodule found on ultrasound
- PTH elevation
91
Primary hyperparathyroidism treatment and prognosis
- Surgical removal - generally unilateral so no general long term issues
- Ethanol or heat ablation - top recommended as easy and better results
○ Ethanol injected into parathyroid nodule to destroy
§ Can be done through skin
- WATCH: - normal gland may be atrophic -> need time to get larger again
○ Hypocalcaemia within 3-6 days in 40% of cases
§ Can lead to neurological issues
- Pre-medicate with Vitamin D
Prognosis is excellent after removal
92
Hypercalcaemia of malignancy what are the two mechanisms, most common tumours in dogs and cats and treatment
```
- TWO mechanisms
○ Osteolysis
○ Paraneoplastic syndrome
§ PTH-related protein is main cause of paraneoplastic hypercalcaemia
- Most common tumours in dogs:
○ Lymphoma
○ Apocrine gland adenocarcinoma
- Most common tumours in cats:
○ Squamous cell carcinoma
○ Lymphoma
- Treatment
○ Treat underlying tumour
○ Prognosis depends on tumour type and treatment
○ Hypercalcaemia is a negative prognostic indicator in lymphoma
```
93
Treatment of hypercalcaemia acute and chronic
- Treat underlying disease
- Acute treatment for hypercalcaemia
○ Fluid therapy(non-calcium containing)
○ Diuretics
○ Prednisolone*
○ Sodium bicarbonate
- Chronic treatment of hypercalcaemia - if cannot treat underlying disease
○ Bisphosphonates
94
On physical exam finding a abnormal kidney size or structure what should you do
- Follow up always important
- May not be associated with overt renal disease
- Early disease recognition and treatment may influence prognosis
95
What are causes of kidney 1. acute size increase 2. acute-chronic size increase 3. chronic size decrease 4. abnormal outline of capsule
```
1. Acute size increase
○ Fluid accumulation
§ Subcapsular or intrarenal haemorrhage
§ Hydronephrosis secondary to obstruction
2. Acute-chronic size increase
○ Hypertrophy secondary to function loss
○ Neoplasia - renal carcinoma, lymphoma
3. Chronic size decrease
○ CKD, renal infarcts
4. Abnormal outline of capsule
○ Renal cysts, renal abscesses
```
96
small or large kidneys what to do with searching for a cause and diagnostic work up
```
Searching for a cause
- Renal size, shape and other factors
- Age of patient
- Chronicity of size change
- Symmetry
- Other clinical signs
- Breed of patient
Diagnostic work up
- Imaging extremely useful
- Functional tests should not be neglected (CBC, serum biochemistry, UA)
- Genetic tests
- Fine needle aspirates or renal biopsy in selected cases
```
97
Identifying proteinuria what are the qualitative and quantitiative tests
```
- Qualitative tests
○ Dipstick
§ Most sensitive for albumin
§ Detection limit 30mg/dL
○ Sulfosalicylic acid
§ Detects all proteins
§ Detection limit 5mg/dL
- Quantitative test
○ Urine protein: creatinine ratio
- non-proteinuric <0.2
- bordeline proteinuric (dog - 0.2-0.5, cat - 0.2-0.4)
- proteinuric (dog >0.5, >0.4)
```
98
What causes urine protein:creatinine ratio changes
```
□ 1. Day-to-day variation
® Day-to-day variation of UPC:
◊ When UPC >4; >35% change = true change in UPC
◊ When UPC ̴0.5; >80% change = true change in UPC
□ 2. Muscle mass of the patient
□ 3. Number of functioning nephrons
□ 4. Urine “contamination”
□ 5. Sampling method
```
99
Why should proteinuria NOT be ignored
- Persistent proteinuria can be a sign of significant renal disease –even without azotaemia
- Pets with proteinuria live shorter than pets without proteinuria - if treat prolong their life
○ More likely to develop azotaemia and uraemic crisis
100
Extra-urinary causes of proteinuria and post-renal urinary proteinuria causes
Extra-urinary causes of proteinuria
- Genital disease
○ Protein ‘leaks’ from genital organs into urine
- Hyperproteinaemia(prerenal proteinuria)
○ Overwhelming of kidney’s filtration and reabsorption capacity
Postrenal urinary proteinuria
- Protein ‘leaks’ into the lower urinary tract
- Inflammation
- Infection
- Trauma
- Bleeding
- Neoplasia
