PU/PD Flashcards
polyuria
excessive volume excretion of urine
pollakiuria
excessive frequency/urgency of urination
dysuria
difficult or painful urination
stranguria
slow, painful urination, caused by muscular spasms of the urethra and bladder
polydipsia
excessive volume drinking
what is the definition (numbers) of polyuria?
> 50 mL/kg/day
very difficult to determine without special metabolic cages or urinary catheterization
what is the definition (numbers) of polydipsia?
> 60-80 mL/kg/day
in the majority of causes, is the patient having primary polyuria or primary polydipsia?
primary polyuria with secondary/compensatory polydipsia
what factors are involved in maintaining water balance physiologically?
- hypothalamus and pituitary: ADH and vasopressin
- kidneys: respond to signals and increase blood volume and plasma osmolality
then thirst center gets activated
what two organs are you concerned about with PU/PD?
brain, kidney
what differential diagnoses would you think of relating to the brain with a PU/PD patient?
- central diabetes insipidus
- primary polydipsia
what differential diagnoses would you think of relating to the kidneys with a PU/PD patient?
- primary nephrogenic DI
- secondary nephrogenic DI
- osmotic diuresis
what does the word diabetes actually translate to?
greek: siphon; to pass through
how common are your differential diagnoses for PU/PD?
central DI: rare
primary polydipsia: less common
primary nephrogenic DI: very rare
secondary nephrogenic DI: common
osmotic-induced diuresis: common
what is the general principle of osmotic diuresis?
ADH is normal or increased, but other osmotic agents keep water from leaving tubule
what are specific rule-outs you should think about with osmotic diuresis?
- diabetes mellitus
- post-obstructive diuresis
- chronic kidney disease
- fanconi’s syndrome
what is the basis of diabetes mellitus?
excess glucose overwhelms renal reabsorption
the pancreas has decreased insulin secretion, too much insulin overwhelms the kidneys’ ability to absorb. Glucose pulls water out: osmotic issue
what is fanconi’s syndrome?
tubular defect prevents various solute reabsorption, including glucose and Na+. get diuresis! receptors defective and can’t pull solutes into cells
basenji’s prone! and small breed dogs
post-obstructive diuresis
“blocked tom cat”
urea can’t get out and accumulates until obstruction relieved
also some tubular damage from pressure
how can chronic kidney disease cause diuresis?
decreased functional nephrons means less urea and sodium reabsorption
also loss of medullary gradient
what is secondary nephrogenic DI? (NDI)
- interference with ADH receptor
- interference with tubule cell function
- lack of medullary gradient
kidney functioning, but something interfering. disease won’t allow for gradient: get medullary washout and can’t conserve water
what osmotic diuresis rule-outs are common?
DM, post-obstructive diuresis, chronic kidney disease are common
fanconi syndrome uncommon
what are the major rule-outs with NDI?
- hyperadrenocorticism
- hypoadrenocorticism
- hyperthyroidism
- pyometra
- hypercalcemia
how does cushing’s cause secondary NDI and thus PU/PD?
- excess of glucocorticoids
- interferes with ADH receptors
- interferes with ADH release
- primary polydipsia?
how does addison’s cause secondary NDI and thus PU/PD?
- lack of glucocorticoids and mineralocorticoids!
- lack of ALDOSTERONE!! responsible for saving Na and dumping K+. leads to Na+ wasting.
- osmotic agent, get medullary washout
how can hyperthyroidism cause secondary NDI and thus PU/PD?
pt in a hypermetabolic state, increased cardiac output, increased blood flow, leads to decreased time for Na reabsorption. this makes for a decreased medullary gradient. primary polydipsia?
how can pyometra cause secondary NDI and thus PU/PD?
pyometra is e.coli bactera: releases endotoxins! this interferes with the ADH receptor by blocking it. PU/PD is often a presenting complaint for pyometra!
how can hypecalcemia cause secondary NDI and thus PU/PD?
interferes with function of ADH receptors and tubular cells
multifactorial and poorly understood!
what are causes of primary polydipsia? what does this lead to?
- hyperthyroidism
- hyperadrenocorticism
- hepatic disease
leads to overhydration and eventual medullary washout
kidneys are usually functioning properly in these cases!
what is psychogenic polydipsia?
learned behavior, usually dogs
what should you be differentiating polyuria from?
pollakiuria
frequency, straining, amount, urgency, blood, changing litter often, night time urination, accidents? etc
what happens to a patient with no ADH?
water channels don’t get inserted into the distal tubules = no water absorption = DIURESIS
what causes central diabetes insipidus?
- partial or complete lack of ADH
- trauma
- neoplasia
- idiopathic
is the polydipsia physiologic or pathologic? what questions should you be asking?
more exercise?
weather changes?
stress?
at water bowl more?
filling water bowl more?
drinking out of toilets recently?
PU/PD is a _________ problem
systemic! need to ask about systemic changes: weight loss, weight gain, V+/D+, neuro signs, sudden blindness?
what is the first diagnostic you should do for a PU/PD patient?
URINALYSIS
assess state of dehydration. if dehydrated, urine should be concentrated. recheck using first morning urine! animals don’t drink at night, and usually will concentrate at night
NEVER WITHOUT WATER! could cause AKI!
if diabetes mellitus is a top differential for a cat you are seeing, what should be something you absolutely should be checking for on a physical exam?
frosty paws!
if a patient’s urine is hypersthenuric, what would their USG be? what would clinical signs be?
dog: USG > 1.030/1.035
cat: > 1.040/45
NOT PU/PD!
what are first wave diagnostics for a PU/PD patient?
urine culture
CBC
biochemistry panel
T4 in cats
abdominal radiographs or US
if even your second wave diagnostics are normal, what next?
rule out:
- psychogenic polydipsia
- medullary washout
- central diabetes insipidus
the dreaded modified water deprivation test
rule out EVERYTHING ELSE before this!
witholding water until 5% dehydrated, if USG still low, give ADH. if USG increases, then you have central diabetes inspidius. if no and it’s still less than 1030, medullary washout or NDI
if all of your first-wave diagnostics are normal, what do you want to rule out?
hyperadrenocorticism: ACTH stim!
hepatic insufficiency: bile acids
cat signalment for diabetes
- males 2x > females
- middle-aged to older cats
- no breed predilection
what species’ diabetes is summarized as insulin resistance?
cats: type 2
no cataracts, frosty paws, neuropathies
clinpath anomaly: profound stress hyperglycemia
need high protein diet and avoid carbs
what is the dog signalment for diabetes?
- females 2x > males
- middle aged: peak 7-9 years
- pedigree analysis: Keeshond
beagles, schnauzers, dachshunds
what are the similarities between cat and dog diabetes?
PU/PD, polyphagia with weight loss. fasting hyperglycemia with glucosuria. predisposed to infections
what species’ diabetes is summarized as lack of insulin?
dogs: type 1
cataracts
need complex carbs
what causes insulin-dependent DM?
type 1: juvenile onset in kids
absolute lack of insulin due to immune-mediated beta cell destruction
what causes non-insulin dependent DM?
- type 2: adult onset diabetes. cats!
relative lack of enough insulin often due to insulin resistance
cats can progress to type 1 (different mechanism)
cats eat dry kibble: constantly getting carbohydrates. have limited glucokinase and can’t process what is there
what can cause insulin resistance in the cat?
- glucose toxicity
- beta cell destruction
- obesity-induced insulin resistance
describe the process of glucose toxicity in cats
chronic hyperglycemia disrupts function of beta cells and peripheral tissues. cells need to let glucose in: only some going in and a lot left out
get impaired insulin secretion from beta cells, peripheral cells have glucose transport down-regulation, and get more hyperglycemia. it is a vicious cycle
describe beta cell destruction in cats
chronic hyperglycemia destroys the beta cell, thus reducing insulin production
to keep up with excessive hyperglycemia, excessive insulin is produced, and then you get chronic hyperinsulinemia. PROBLEM: amylin!
what protein is secreted with insulin? why is it troublesome?
amylin! co-secreted with insulin. amylin gets converted to amyloid, which is re-deposited in beta cells and over time, you get destruction of those cells. amylin leads to insulin resistance by negative feedback
no more insulin production = type 1!
describe obesity-induced insulin resistance
circulating fatty acids induces insulin resistance in peripheral tissues. can see:
1. insulin receptor down-regulation
2. impaired binding: insulin bounces off receptor
3. impaired signaling: prevents GLU from being put through
what are the counter-regulatory hormones for insulin? what could be causing these to counter-act insulin?
Epinephrine - INFECTIONS AND INFLAMMATION
Cortisol - INFECTIONS, inflammation, cushing’s, steroids
Progesterone - pregnancy/heat! gestational diabetes!
Growth Hormone - acromegaly in cats!
Glucagon - glucagon-secreting tumors, rare
Thyroid Hormone - hyper AND hypothyroidism
Obesity-induced (multi factorial)
what species can get acromegaly from growth hormone?
cats
can cats with diabetes get cataracts?
no! frosty paws and neuropathies: plantar-grade stance walking on hocks
what do you really need to be careful of when suspecting a cat is diabetic?
STRESS HYPERGLYCEMIA! make sure it’s not spill-over from stress. can be profound in cats
up to 350-400 mg/dL
spill-over threshold of kidneys: 250-28-mg/dL.
in cats, hyperglycemia + glucosuria =
NOT DIABETES MELLITUS! need to differentiate is it DM vs stress hyperglycemia!!
how do you differentiate between stress hyperglycemia and DM?
fructosamine: glucose bound to albumin. irreversible and stays in body as long as albumin hangs around. glucose doesn’t come off until albumin is cleared.
differentiates chronic hyperglycemia from acute hyperglycemia
what are classic signs of DM?
polyuria, polydipsia, polyphagia, weight loss
what is the baseline diagnosis for DM?
- FASTING hyperglycemia
- glucosuria
general treatments for DM
- insulin, diet, exercise
- additional: concurrent illness txt, cataract sx
what are the differences between dog and cat diets?
dogs: complex carbs and fiber with moderate, regular exercise
cats: protein and low carbs: avoid carbs!
how do we categorize insulin?
short, intermediate, long duration
crystalline, protamine, analog type
most of the time, what type of insulin is used?
regular crystalline: short lasting
also analog: lispro, aspart
what are the short-lasting insulin types?
crystalline: regular
analog: lispro, aspart
what are the intermediate-lasting insulin types?
crystalline: lente
protamine: NPH
what are the long-lasting insulin categories?
protamine: PZI
analog: glargine, detemir
what are the different types of insulin brand names?
short-lasting: crystalline: humulin-R, novalin-R
intermediate-lasting: crystalline: vetsulin, protamine: humulin-N, novalin-N
what type of insulin is vetsulin?
intermediate-lasting crystalline lente
what insulin is used for DKA?
regular!! short-lasting and crystalline. only used in-hospital!!
what type of insulin is prozinc?
long-lasting protamine PZI
what is the first choice maintenance insulin for dogs?
VETSULIN BID!!
always given SQ twice daily!! every animal should be started on insulin BID no matter species or type!!
what is the first choice maintenance insulin for cats?
Glargine BID!!
PZI is also good
given SQ twice daily!!
how is regular insulin for DKA given?
IM or CRI! don’t want to give SQ because normally patients are dehydrated and would get poor absorption
what oral hypoglycemics are actually approved for cats?
SLGT2 inhibitors: velagliflozin, bexagliflozin
why would traditional oral hypoglycemics not work in cats?
glucose toxicity!! may increase insulin secretion, and may already be type 1. in cats when they have too much glucose, the beta cells are releasing more and more insulin, but amyline is also being released, which is destroying the beta cells.
why would traditional oral hypoglycemics for dogs not be good?
MOA: decrease peripheral insulin resistance and/or increase insulin secretion
issue with dogs: dogs are Type 1 diabetics, so they have autoimmune destruction of beta cells so they will never produce insulin. if you have no insulin, it doesn’t matter if you are increasing insulin sensitivity. these are not effective because the pancreas
how does Gliflozin work?
glucose FLOWS in urine
proximal renal tubules: prevents glucose reabsorption
in a normal cat, sodium cotransporters reabsorb glucose. SGLT2 gets most of it, and SGLT1 gets the rest. in a diabetic cat, the receptors are upregulated and reabsorb more glucose!! at some point you overflow the threshold. the animal then perceives starvation and tries to increase glucose
in what patients can you NOT use oral hypoglycemics for? why?
- requires SOME functional beta cells!
- cannot be type 1
- cannot use if previous or current DKA; pancrease is likely injured at this point
- can develop euglycemic DKA
summarize oral hypoglycemics in a diabetic cat. what do you need to be aware of?
- lowers serum glucose quickly
- reverses glucose toxicity
- reduces insulin hypersecretion
requires SOME functional beta cells! cannot be a type 1!! cannot use if previous or current DKA. can develop euglycemic DKA
how do the oral hypoglycemics prevent hypoglycemia in cats?
primarily inhibits SGLT2 cotransporter to prevent glucose reabsorption. but there’s another receptor that gets the rest of it: SGLT1! maintains some glucose reabsorption and prevents severe hypoglycemia
what do you really want to be monitoring with diabetes patients?
clinical signs! decrease in PU/PD, decrease in appetite, stabilization of weight loss
what does a glucose curve tell you?
- insulin duration
- insulin effectiveness
- glucose nadir (low point)
what should a glucose curve look like?
appropriate duration: 12 hours
appropriate time of nadir: 6 hours
dogs: 80-200mg/dL
cats: 80-300 mg/dL
range at nadir: 80-100mg/dL
how do you do a glucose curve collection?
in hospital: every 2-4 hours
at home: freestyle libre continuous sampling
