metabolism 4

Question 1

What are the 3 steps in renal insufficiency at what percentage loss of function occur and what occurs at each stage

Answer 1

1) Regulatory failure
- Loss of ≥66% of nephron function
- Failure to concentrate urine→ polyuria
- Metabolic acidosis and electrolyte abnormalities
2) Excretory failure
- Loss of ≥75% of nephron function
- Nitrogen wastes accumulate
3) Biosynthetic failure : Erythropoietin
Non-regenerative Anaemia

Question 2

List 3 causes of primary renal damage and 4 causes of secondary renal damage (decreased tubular function)

Answer 2

Primary
1) Toxic insult – ethylene glycol, grapes, lillies
2) Parenchymal damage and fibrosis - inflammation and infectious process
3) Nephritis - inflammation of the kidneys
Secondary
1) Primary diabetes insipidus - failure to excrete ADH
2) Secondary diabetes insipidus
3) Hypercalcemia, Hyperadrenocorticism, Pyometra
4) Loss of medullary concentration gradient – depletion of NaCl and urea
○reversible

Question 3

List the 4 ways renal function is assessed and what is tested within each test

Answer 3

1) Excretion of waste products
- Urea and Creatinine in mammals
- Uric acid in birds and reptiles
- SDMA
2) Fluid and electrolyte balance - dehydration
- Urine concentration
- Serum and urine electrolytes
3) Acid-base regulation - Acidosis, alkalosis
- Serum bicarbonate
- Urine pH
- Blood pH and blood gases
4) Production of erythropoietin
- RBC count/PCV/Haemoglobin or measure EPO

Question 4

How do you measure GFR in urinalysis

Answer 4

Measurement of Glomerular Filtration Rate (GFR) - don’t measure directly but indirectly through the 4 methods of assessing renal function

Question 5

List 6 uraemias

Answer 5

1) Mucosal ulceration
2) Halitosis - bad breath
3) Vomiting
4) Depression
5) Weakness
6) Anorexia

Question 6

Describe the 3 broad causes of azotaemia and examples within

Answer 6

Prerenal
Decrease Renal blood flow - something upstream
- Dehydration - reduced blood volume
- Severe haemorrhage
Renal
- decrease in functional nephrons, decrease GFR
Postrenal
Decrease urine output- get leakage of urine into abdomen and contents reabsorbed into circulation
- Tumour, inflammation - nephrosis
- Urinary tract disease
- Obstruction - kidney stones

Question 7

urea filtration, reabsorption where occur and what are the 2 sources of urea

Answer 7

• Sources
  1) Liver protein catabolism → ammonia → urea
  2) Large intestine (small amount)
• Freely filtered by glomerulus
• Some tubular reabsorption - especially with slower urine flow

Question 8

What are the two main reasons serum urea increases and give examples within

Answer 8

1) ↓ glomerular filtration rate
- Decreased renal perfusion = prerenal
- Loss of nephron function = renal
- Obstruction of urine flow = postrenal
2) ↑ increased protein breakdown - prerenal
- High protein diet
- GI bleeding into the gut - increase protein breakdown in the gut, increase microbe convert to ammonia and liver convert to urea and excret into circulation on its way to the kidney
- Protein losing enterophathy

Question 9

Which is more specific for pre-renal azotaemia urea or creatinine

Answer 9

Urea increases more with pre-renal azotaemia than creatinine increases - less specific

Question 10

What are the 3 main downfalls of using urea as a measurement of azotaemia and why

Answer 10

1) Less useful in assessing renal function in ruminants and horses - use creatinine mainly
- Ruminants excrete urea via rumen
- horses excrete urea via large intestine
- Excretion depends on nitrogen intake
2) Not useful in birds and reptiles
- Protein catabolism →ammonia → uric acid
3) Increases can reflect dehydration

Question 11

creatine filtration, excretion and reabsorption and why more specific then urea but what animal not used in

Answer 11

• Freely filtered by the glomerulus
• Small amount excreted in GIT
• No tubular reabsorption - more specific → better indicator of decreased GFR than urea
• Concentration not affected by diet
  not used in birds as only see once advanced renal disease

Question 12

List the 3 main reasons see increase serum creatinine and 1 decrease and examples within

Answer 12

1) ↑ muscle mass → ↑ creatinine
- Greyhounds are higher than labrador
2) ↑ muscle breakdown → ↑ creatinine
- Training or rhabdomyolysis
- When stable with weight and muscle turnover most effective
3) ↓GFR
- Decreased renal perfusion = prerenal
- Loss of nephron function = renal
- Obstruction of urine flow = postrenal
4) Decreases with generalized muscle wasting
- Could mask kidney disease as if occurring at same time one make go up either decrease so overall no change

Question 13

What is the downside with creatinine

Answer 13

• Little change in creatinine until advanced renal failure
• normal creatinine doesn’t mean don’t have renal dysfunction
• need to explore early onset markers

Question 14

uric acid in birds and reptile list 4 things that increase uric acid and why difficult to use

Answer 14

1) Renal disease (low sensitivity) - only really see increase in advanced renal disease
2) Profound dehydration - prerenal
3) Ovulation - very hard to know
4) Diet (high protein)
difficult
- Higher levels are seen in carnivorous species
- Hard to get good reference intervals

Question 15

SDMA what does it stand for, when released, when increased levels seen and what causes increase levels

Answer 15

• Symmetrical dimethylarginine
• Released with proteolysis and excreted through the kidneys
• Increased levels are seen with ≥ 40% loss of renal function
• Slightly higher levels are seen in Greyhounds
• Increases with any cause of decreased GFR
  e. g. dehydration, hypovolaemia (pre-renal)

Question 16

List 3 clinical signs of renal azotaemia and pre-renal azotaemia

Answer 16

renal azotaemia
1) Polyuria and polydipsia
2) Anuria or oliguria
3) Inadequately concentrated urine
Pre-renal azotaemia
1) Concentrated urine - actively resorbing water
2) Evidence of dehydration
○ Vomiting, decrease skin turgor, dry tacky membranes, increase in urea and creatinine
3) Evidence of increase protein breakdown in GIT
○ Melena - blood in faeces
○ Increase in urea only, creatinine will be normal

Question 17

Urine Specific gravity what measure with, what is it, what does it indicate and what does it reflect

Answer 17

• Refractometry
  ○ If above 1.000 greater than water (always the case with urine)
  ○ USG is ratio of refractive index of urine compared to water
  ○ Indication of tubular function = ability of tubules to absorb or excrete water
  ○ Reflects urine osmolality
• High USG = more concentrated urine
• Low USG = less concentrated urine

Question 18

What are the 3 ways to measure fluid and electrolyte balance

Answer 18

1) Urine specific gravity
2) Dipstick reagent pad
3) urine osmolality

Question 19

1) If have azotaemia + concentrated urine =

2) Azotaemia + inadequate urine concentration =

Answer 19

1) = dehydration - prerenal

2) = renal

Question 20

List 5 factors that influence urine concentration

Answer 20

1) Number of functional nephrons
2) Renal medullary hypertonicity
○ Resorption of NaCl & Urea
○ Renal medullary blood flow
3) ADH secretion and action - RAAS mechanism
- Extra-renal factors
○ Hydration status
○ Serum electrolytes
○ Concurrent diseases - inhibiting ADH function - diabetes insipidus
○ Drug therapy e.g. diuretics
4) renal insufficiency as unable to conserve water and electrolytes and unable to excrete N wastes

Question 21

what are the 3 things that urine concentration does not distinguish

Answer 21

1) reversible from irreversible
2) acute from chronic renal disease
3) primary from secondary renal insufficiency

Question 22

Progression of renal insufficiency what do you see:

1) ≥ 40% loss of function →
2) ≥ 66% loss of function →
3) ≥ 75% loss of function →

Answer 22

1) ↑ SDMA
2) polyuria
3) azotaemia

Question 23

postrenal azotaemia findings of examination, history and histology

Answer 23

• History – stranguria or dysuria
• Examination/imaging findings:
  ○ Decreased urine output - leaking into abdomen or banking into the bladder
  ○ Distended bladder - pressure can build back to the kidney causing kidney disease
  ○ Uroabdomen
  Hyperkalaemia - increase in potassium

Question 24

What are the 2 main causes of postrenal azotaemia and examples within

Answer 24

1) Obstruction of urine flow
○ Urinary calculi - urinary stones could be suck in urethra
○ Urethral plug
2) Internal urine leakage/uroabdomen
○ Ruptured bladder - can be seen with contrast leaking into abdomen in radiograph
○ Torn ureter / urethra
○ Patent urachus

Question 25

List the other 8 changes with renal insufficiency

Answer 25

- Potassium - Phosphate - Sodium - Chloride - Bicarbonate - Albumin - Anaemia - Amylase and Lipase

Question 26

potassium what causes increase and decrease

Answer 26

``` - Hyperkalaemia - Anuric (acute kidney injury), oliguric or obstructive disease (post-renal) ○ Decreased GFR ○ Decreased secretion ○ Associated acidemia - Hypokalaemia - Polyuric renal disease ○ Increased urine flow rate ○ Reduced tubular function - chronic kidney disease → decreased potassium absorption ```

Question 27

phosphate what causes with increase and decrease

Answer 27

- Hyperphosphataemia ○ Decreased GFR - renal (generally more severe) ○ Bone activity (young animals) - also get high ALT ○ Sample haemolysis - pre-renal - Hypophosphataemia common in horses with chronic kidney disease uncommon in other species

Question 28

calcium what occurs with chronic kidney and acute kidney disease

Answer 28

Chronic Kidney Disease → Hypocalcaemia in dogs and cats, rarely hypercalcaemia - secondary to hyperphosphatemia and decreased Vitamin D production → Hypercalcaemia in horses and rabbits - High calcium diet - Renal excretion controls excess and when get disease hard to keep up with the calcium absorbed from the gut Acute Kidney Injury → Hypercalcaemia or Hypocalcaemia

Question 29

magnesium what occurs with decreases GFR

Answer 29

Decreased GFR - Hypermagnesaemia | - Don't have on a routine biochemistry

Question 30

sodium and cholide when elevated

Answer 30

- Elevated with dehydration - Variable level with renal insufficiency ○ Depends on water loss vs electrolyte loss ○ Changes masked by dehydration ○ Selective Cl loss with vomiting

Question 31

bicarbonate what does renal insufficiency cause and what are the two types

Answer 31

- Renal insufficiency causes a metabolic acidosis 1) Titrational acidosis - ureamic acids +/- Lactic acid 2) Secretory acidosis – renal loss of bicarb → Hypobicarbonataemia

Question 32

amylase and lipase what are they

Answer 32

- Pancreatic enzymes - Excreted by the kidneys - Decreased GFR → ↑ amylase and lipase

Question 33

What are the features of acute kidney injury and chronic kidney disease

Answer 33

Acute Kidney Injury (AKI) = abrupt decline in renal function (hours to weeks) - (acute renal insufficiency) - Have dysfunction but often reversible to the extent that the animal can live a healthy life - Toxins, infection, drugs Chronic Kidney Disease (CKD) = progressive decline in renal function over months to years - (chronic renal insufficiency) - Tends to be non-reversible

Question 34

List two secondary renal insufficiency causes

Answer 34

1) Hyperadrenocorticism - cushings disease dogs → impaired tubular response to ADH 2) Diabetes insipidus → impaired ADH secretion (central DI) → ↓ tubular response to ADH (nephrogenic DI)

Question 35

List 5 causes of urinary protein

Answer 35

1) Renal - Glomerular loss - ↑ filtered protein - Tubular dysfunction - ↓reabsorbtion 2) Inflammation of urinary tract - Cystitis - Pyelonephritis 3) Haemorrhage 4) Genital tract - Prostatic disease - Uterine or vaginal disease 5) Prerenal - Physiologic e.g. dehydration, fever - Hyperglobulinaemia, haemolysis, myopathy (a disease of muscle tissue)

Question 36

What are the two sources of protein leakage within the kidney and which is more severe

Answer 36

1) Glomerular - excess filtration due to leaky glomerulus ○ Often higher level of proteinuria ○ Primarily Albumin 2) Tubular - less severe than glomerular ○ Milder proteinuria ○ Albumin and other proteins eg aminoacids ○ May see other evidence of tubular dysfunction eg renal glycosuria

Question 37

List the 4 ways proteinuria is assessed and what do you need to rule out first before do any of these assessments

Answer 37

1) urine dipstick 2) urine sediment examination 3) urine protein:creatinine ratio 4) microallbuminuria Need to rule out inflammation as a source of the increase in protein first

Question 38

urine dipstick what most sensitive to, what effected by and when use urine sediment examination

Answer 38

- Urine dipstick ○ Most sensitive to albumin ○ Affected by urine temp, colour, pH, storage, contaminants - Urine sediment examination ○ Cytology evaluation for haematuria, pyuria (WBC), bacteriuria and casts

Question 39

microallbuminuria when detects, what useful for, why not usually used

Answer 39

○ Early detection of renal disease before there is overt proteinuria (i.e. dipstick protein is negative) ○ Useful for screening predisposed breeds ○ Positive with high levels of exercise and so not normally done

Question 40

How to differentiate between acute kidney injury vs chronic kidney disease

Answer 40

- Magnitude of azotaemia does not differentiate - Need knowledge of: •Duration of clinical signs •Urine output •Calcium and Potassium levels •Other clues eg anaemia (RBC have long half-life so take awhile to see decrease in RBC when erythropoietin has been decrease), weight loss

Question 41

what see in blood and clinical signs of chronic kidney disease

Answer 41

- Hypocalcaemia in dogs and cats (only 5-10% hypercalcaemic) - Hypercalcaemia in horses - Hypokalaemia common in cats - Anaemia occurs with chronic renal failure ○ ↓erythropoietin - Chronic polyuria and polydipsia - May see weight loss

Question 42

what see in blood and clinical sings, history acute kidney injury

Answer 42

- May see hypercalcaemia or hypocalcaemia in dogs and cats - Hyperkalaemia if anuric or oliguric - Usually not anaemic - Acute history of illness

Question 43

What are the 4 routine urinalysis and what are the 2 additional testing

Answer 43

``` Routine urinalysis 1) Direct observation 2) Urine specific gravity (USG) 3) Urine dipstick 4) Urine sediment examination Additional testing 1) Urine protein:creatinine ratio (UPC) 2) Urine culture ```

Question 44

what does the following colours of urine indicate | red, brown, dark yellow

Answer 44

- Red = haemoglobin or haemorrhage - can be common in rabbits - Brown = Myoglobin, haemorrhage, bilirubin - Dark yellow = concentrated or bilirubin

Question 45

what does the clarity of urine indicate and what species has very cloudy urine and why

Answer 45

varies with species Cloudiness can reflect - for - Mucus - Cells (pyuria) – leukocytes or epithelial, casts - Crystals – especially horses and rabbits - Bacteria - Storage horse and rabbit it is crystals and mucus

Question 46

Urine sample storage and handling how long until perform testing, how to store and what to do before testing

Answer 46

- Collection should precede treatment - Perform urinalysis within 30 minutes so best in clinic - Can refrigerate up to 12 hours ○ May introduce crystals and alter pH ○ Bring to room temperature before testing

Question 47

List the 4 methods of urine collection and what useful for

Answer 47

1) cystocentesis - least likely for contamination useful for dogs and cats 2) catheterisation - must use sterile technique 3) voided (free catch) - not sterile, midstream best, mainly dogs and cats good for USG 4) off the floor/litter tray - useful for USG

Question 48

List the 7 things urine dipsticks assess

Answer 48

- Urobilinogen - Protein - pH - Blood - Ketones - Bilirubin - Glucose

Question 49

Protein on the dipstick when get false positives and when positive results more significant and why

Answer 49

- False positives with alkaline urine (pH > 8.0) - so need to confirm with another test - Positive results more significant in dilute urine ○ As if detect trace amount of protein means more protein is being lost as large amount of urine

Question 50

What are the 2 other ways of assessing proteinuria if suspect false positive with alkaline urine

Answer 50

1) Sulfosalicylic acid precipitation test - detects all proteins - use with alkaline proteinuria 2) UPC

Question 51

causes of glucosuria

Answer 51

○ Hyperglycaemia 1) exceeding renal threshold 2) Tubular disease (renal glucosuria)

Question 52

ketones when see in urine, which ketone more sensitive, what one is major in the blood and which first ketonuria or ketonaemia

Answer 52

- Only really see in if catabolic state or ketosis (cattle, horses) and diabetes mellitus (dog and cat) - Detects: acetone (most sensitive) and acetoacetic acid - Dipstick does not measure β-hydroxybutyrate - measured in the blood ○ (Major intermediate in ketosis) - Ketonuria often precedes ketonaemia

Question 53

bilirubin is it significant to find in a cat or a dog

Answer 53

- Dogs lower renal threshold - conjugate bilirubin in tubules - not really significant finding - Bilirubinuria in cats is always significant

Question 54

blood in the urine what are the 3 possible sources and the 3 ways to differentiate between them

Answer 54

- Reacts with haemoglobin (infection, RBC lysis), myoglobin (muscle breakdown), and intact erythrocytes - Differentiation of cause 1. Sediment exam - is there intact RBCs 2. Plasma colour & CBC results - myoglobin has brown tinge 3. CK levels – increased with myopathy

Question 55

urine pH what increases and decreases with normally and what does it affect

Answer 55

- Acidic pH (7.0) vegetable diet - Post-prandial “alkaline tide” in dogs and cats ○ Straight after eating generally get pH increasing before normalising - Affects type of crystals and uroliths

Question 56

urobilinogen how formed, what does presence in urine indicate, is there variation

Answer 56

- Formed in intestine by bacterial breakdown of conjugated bilirubin - Presence indicates patent bile duct - Correlation of increase and hepatobiliary disease is poor in animals - Does vary quite a lot so don't always use

Question 57

What are the 3 things to ignore on a dipstick

Answer 57

1) nitrite 2) leukocytes 3) USG

Question 58

what stain used in urine sediment evaluation

Answer 58

Can use Sedi-stain to stain the cells and bacteria however should make one stained and one unstained

Question 59

What are the 6 things you can find within a urine sediment

Answer 59

1) cells 2) fat globules 3) casts 4) crystals 5) fungal hyphae 6) parasite eggs

Question 60

what are the 3 types of cells found in urine and types within

Answer 60

- Erythrocytes - Leukocytes - Epithelial cells ○ Urothelial ○ Squamous ○ Caudate (tubular) ○ Sperm ○ Prostatic

Question 61

What are the 4 type of casts and types within

Answer 61

1) Hyaline cast 2) granular cast 3) waxy cast 4) cellular cast - epithelial - erythrocyte - leukocyte

Question 62

Urinary tract neoplasia name some main ones

Answer 62

- Urothelial (transitional) cell carcinoma - most common and often aggressive - Prostatic carcinoma - Squamous cell carcinoma - of the bladder or urethra - Leiomyoma - arise from bladder - Leiomyosarcoma - arise from bladder

Question 63

What occurs to globulin concentration in a dog with hepatic insufficiency, why and when else does this occur and what other changes would you see on biochemistry

Answer 63

Decreased serum concentration of globulins ○ Inflammation increase globulins like fibrinogen due to increased risk of infection without liver and kupffer cells removing microbes form the gut - also see with PSS Other changes - decreased albumin, glucose, cholesterol in serum - increase in bile acid concentration in serum