1
Q
Processes that regulate urine formation
A
- glomerular filtration (passive)
- tubular absorption (active or passive)
- tubular secretion (active or passive)
2
Q
Glomeruli
A
- capillary endothelium
- basement membrane
- glomerular epithelial cells (podocytes) with foot processes
3
Q
Evaluation of glomerular filtration
A
- excretion of substances that pass freely thru the glomeruli –> size <2.4 - >3.4, positive charged passes more freely
- albumin is 3.5 nm and negatively charged –> not present in urine of cats, cattle, horses, in low conc in dogs
4
Q
Glomerular filtration rate
A
Fluid that goes from plasma to glomerular filtrate
- assessed by rate some substances are cleared from the plasma
- GFR depends on renal plasma flow
- RPF depends on blood volume, cardiac output, # of functional glomeruli, constriction/dilation of afferent/efferent arterioles
- other: intracapsular hydrostatic pressure, oncotic pressure
5
Q
The ideal biomarker for GFR
A
- not bound to protein
- pass freely through filtration barrier
- neither excreted nor absorbed by renal tubules
- insulin, iohexol, manitol nearly meet the criteria
- creatinine is secreted very little and meets criteria
- imagining can be used
6
Q
Function of renal tubules is assessed comparing ___________
A
The urinary excretion of a plasma substance to insulin
- if greater than insulin –> there is tubular secretion, and if lower there is resorption or does not pass freely though filtration barrier
7
Q
Na
A
75% resorbed in proximal tubules
- passively resorbed in loop of Henle
- ADH stimulates absorption in the loop of Henle
- aldosterone stimulates absorption in the collecting ducts
8
Q
Cl
A
75% resorbed in the proximal tubules
- passivley resorbed in the loop of Henle
- resorbed passively in distal nephron due to a gradient formed by Na
9
Q
HCO3
A
90% conserved in the proximal tubules via H secretion
- collecting ducts type A intercalated cells increase resorption
- collecting ducts Type B intercalated cells decrease resorption when there is excess
10
Q
K
A
Most is resorbed prior to distal tubules
- secreted by principal cells in collected ducts (promoted by aldosterone)
- movement into tubules enhanced by high flow and inhibited by low flow
- ADH promotes secretion in cortical collecting ducts
11
Q
H
A
Secreted by type A intercalated cells in distal nephron
- aldosterone and acidemia promote secretion
- limited amount secreted in proximal tubule
- most renal secretion of H is within NH4 and either HPO4 or H2PO4
12
Q
Ca
A
80-85% resorbed in proximal tubules and loop of Henle
- PTH promotes resorption
- vit D promotes resorption
13
Q
PO4
A
85-90% resorbed in proximal tubule
- enhanced by hypophosphatemia and insulin
- inhibited by hyperphosphatemia and PTH
14
Q
Mg2
A
Near all resorbed in the loop of Henle
- ADH, PTH, glucagon, calcitonin and B-agonists stimulate resorption
15
Q
Glucose
A
All resorbed in proximal tubules
- mechanism involve transporter proteins that can be overwhelmed by high saturation of plasma glucose (glucosuria)
16
Q
Proteins and amino acids
A
Nearly all resorbed in proximal tubules
- AA use 7 different transporters for 7 AA groups
- larger proteins (inclu albumin) enter the tubular cells by endocytosis and are degraded to amino acids
17
Q
What are 3 important receptors mediating endocytosis?
A
Megalin, aminionless, and cubalin
18
Q
Urea
A
60-65% resorbed in proximal tubules
- ADH enhance resorption in distal nephron
- responsible for 50% of hypertonicity of the medulla
19
Q
Creatinine
A
Small amounts are secreted in proximal tubules (dogs)
- does not happen with horses and cats
20
Q
Water
A
30% of renal perfusion flow becomes ultrafiltrate, 75% is passively resorbed in proximal tubules
- passively resorbed in the loop of Henle as it enters hypertonic medulla
- collecting ducts are permeable in presence of ADH thru aquaporin
21
Q
_____ is imperbeable to water
A
Ascending loop of Henle
22
Q
Concentrating ability
A
Ability to resorb water in excess to resorption of solutes
- will increase osmolarity
23
Q
Diluting ability
A
Ability to resorb solutes in excess to resorption of water
- will decrease osmolarity
24
Q
Isosthenuria
A
Urine osmolality is the same of plasma osmolality
- USG 1.007-1.013
25
Hyposthenuria
Urine osmolality is less than isosthenuric values
26
Eusthenuria
Osmolality that is expected for an animal with adequate renal function
- around hyposthenuria
27
Hypersthenuria
Very concentated urine
28
Urine concentration
ADH must be present!
- stimuli: hyperosmolality, decreased cardiovascular pressure, increased angiotensin (less extent)
- epithelial cells of distal nephron must be responsive to ADH
- concentration gradient: medulla osmolality must be greater than that of the fluid in the tubules
29
Urine dilution
Na and Cl must actively transported from the tubular fluid to the interstitial fluid by epithelial cells in the ascending loop of Henle
- very little water removed by the distal nephron
30
With chronic renal insufficiency, renal tissue is _______
Inadequate to maintain health
31
At ____ of normal GFR, animal is clinically healthy but animal has less tolerance to insults
50%
32
Chronic renal failure has a GFR of ______
20-50% of normal
- azotemia and anemia appears
- polyuria due to decreased concentrating ability
33
CRF - symptoms
- hypocalcemia (not in horses)
- metabolic acidosis --> kidneys can't regulate fluid volume or electrolyte balance
- uremia
- neurologic, GI, cardio complications
34
End-stage renal failure
GFR is <5% of normal
| - terminal stages of uremia with oliguria or anuria
35
When more than ___ of the nephrons are lost, the animal loses the ability to concentrate urine
2/3
36
When more than ____ of the nephrons are lost, the animal becomes azotemic
3/4
37
Reasons for loss of concentrating ability
- more solutes presented to remaining nephrons --> solute diuresis
- medullary hypertonicity is not maintained --> medullary tissue is damage or blood flow is abnormal, decreased Na/Cl absorption in ascending loop of Henle, damaged cells in distal nephron less responsive to ADH
38
Polyruia in chronic renal insufficiency or failure
Not as severe as in diuretic states (ex: diabetes insipidus)
- GFR is decreased --> decreased filtered volume
- polyuria precedes azotemia (cats can concentrate more than other species, may be able to keep more concentrating ability along with azotemia)
- progression of renal disease and nephron loss leads to oliguria or anuria
39
Evidence of insufficiency or failure
- azotemia: increased BUN or creatinine on plasma due to decreased GFR
- low USG due to loss of concentrating ability
40
Evidence of chronicity
Clinical findings including duration of signs
| - lab findings: anemia, hypocalcemia (may also occur in acute renal failure, or hypercalcemia in horses)
41
Acute renal failure
Reversible, or irreversible, abrupt (hours or days), disease or insult that markedly decreases GFR
- usually toxicants, renal ischemia or infections
42
Azotemia
Magnitude of azotemia does not differentiate acute from chronic (is mild to severe in both cases)
- occurs more rapidly in acute (days), than in chronic renal failure (weeks to months)
43
Acute renal failure - urine volume and USG
Abrupt nature of acute failure --> no time for nephron hypertrophy --> very low GFR --> oliguria or anuria
- urine may be concentrated if formed before insult
- may be isosthenuric
- not expected to be hyposthenuric!!
- acid base and electrolyte status may become abruptly abnormal (hyperkalemia and acidemia)
44
Increased BUN and/or creatinine
Azotemia
45
Uremia
Urinary constituents in blood --> clinical signs reflecting renal failure
- vomiting, diarrhea, coma, convulsions, ammoniacal odor on breath
46
Pre-renal azotema pathogenesis
Any process that decreases RPF --> decreases GFR --> volume receptors sense reduced blood flow --> triggers angiotensin-renin system --> angiotensin 2 constricts afferent and efferent glomerular arterioles --> further decreases GFR
- hypovolemia --> increase Na absorption and water in proximal tubules --> increased BUN passive resorption --> decreased flow rate --> more time for resorption
47
Azotemia in face of protein losing nephropathy and hypoalbuminemia
Decreased oncotic pressure --> hypovolemia
48
Clinical hypoadrenocorticism
Aldosterone deficiency --> hyperkalemia --> decreased CO --> decreased arterial bp --> decreased GFR, increased loss of Na --> increase water loss --> hypovolemia
49
Severe intestinal hemorrhage causes
Pre-renal azotemia
50
Renal azotemia
Any renal disease that leads to major decreased GFR
- loss of nephrons
- decreased vascular potency within kidneys
- decreased glomerular permeability
- increased renal interstitial pressure
- increased intratubular pressure
51
Renal azotemia - pathogenesis
Loss of 65-75% of the nephrons --> decrease GFR --> azotemia
| - processes that contribute for pre-renal may also be present
52
With post-renal azotemia, the cause of increased BUN/creatinine is ______ to the nephron
Distal
53
Pathogenesis of obstructive azotemia
Release of vasoactive substances --> constrict glomerular arterioles --> decrease GFR
- impaired flow --> increased intracapsular pressure --> decreases GFR --> as less ultra filtrate is formed intracapsular pressure tends to decrease
54
Pathogenesis of azotemia caused by leakage of urine within the body
Leakage in peritoneal cavity --> BUN and creatinine enter plasma via passive diffusion thru mesothelium (BUN equilibrates faster than creatinine)
- leakage in tissue surrounding urinary tract --> diffusion from extra to intravascular azotemia
- if intestinal excretion of BUN/creatinine does not compensate decreased urinary excretion --> azotemia
- processes that lead to pre-renal or renal azotemia may be present
55
Increased urea production
Increased proteolysis --> generates more NH4 --> increased urea synthesis by hepatocytes
- if rate of urea prodcution exceeds rate of urea excretion --> azotemia
- renal reserve --> increased excretion of increased BUN --> mild-no azotemia
- intestinal hemorrhage = high protein diet + hypovolemia
56
Azotemia and uremia criterion involves _____
USG
- renal and extrarenal factors that may affect concentrating ability must be considered
- exclusively pre renal --> ADH simulus (>1.030 in dogs, >1.040 in cats, >1.025 in horses/cattle)
57
If USG below those values and no evidence of increased urea production _______
Then there is loss of concentration ability
58
USG in renal disease
1. 007-1.013 due to tubulointerstitial impairment and loss of nephrons
- USG may be >1.013 but still inappropriately low if: decrease GFR more than tubular function, high urine concentration of glucose (USG overestimated), plasma osmolality is increased
59
Extra-renal
Azotemia develops from hypovolemia
- distal nephron not responsive to ADH (nephrogenic diabetes insipidus)
- solute overload: too much solute entering the loop of Henle --> high flow rate --> decreased absorption of fluid
60
Decreased medullary hypertonicity
- prolonged hyponatremia or hypochloremia
- blocked sodium and chloride
- decreased urea production due to liver disease
- solute overload or prolonged diuresis
61
Urea nitrogen concentration in plasma
Many labs report urea directly, but frequently reported based on its nitrogen content
- sample: serum or plasma
62
Increased urea nitrogen due to decreased excretion
```
Pre-renal:
- hypovolemia, decreased CO, shock
Renal:
- inflammatory
- amyloidosis
- toxic nephrosis
- renal ischemia/hypoxia
- congenital
- hydronephrosis
-neoplasia
Post-renal
- obstruction, leakage
```
63
Increased urea nitrogen due to increased production
- intestinal hemorrhage
- dietary
- increased catabolism
64
Decreased urea nitrogen due to hepatic insufficiency
Extensive hepatocellular damage (>80%) --> impaired urea cycle --> decreased UN and increased NH4
65
Decreased urea nitrogen due to portosystemic shunt
- less NH4 delivered to hepatocytes
| - less uptake of NH4 by hepatocytes (atrophy, necrosis or fibrosis)
66
Decreased urea nitrogen due to increased urea excretion
Less water resorption (ex: osmotic diuresis) --> less concentration gradient --> less urea is reabsorbed
- central and nephrogenic diabetes insipidus lack of ADH activity --> less urea and water resorption
67
Urea is responsible for ____ of medulla hypertonicity
50%
- decreased urea resorption --> decreased medulla hypertonicity --> decreased concentration gradient --> decreased concentration ability --> polyuria --> dehydration/hypovolemia --> azotemia
68
Creatinine concentration on serum or plasma
- sample: serum or plasma, up to 4 days at RT and 1-3 months -20C
- test: dry chemistry and wet, colorimetric
69
Increased creatinine concentration due to decreased GFR
Process may be pre, renal or post renal
70
Increased creatinine due to increased production and release from myocytes
- only if excretion is impaired (ex: rhabdomyolysis in horses)
71
Increased creatinine is common in
- greyhounds
| - neonate foals if placenta clearance is not adequate (should disappear after birth)
72
Decreased creatinine
Not clinically significant
- decreased muscle mass
- hypoproteinemia (slightly decreased)
73
Creatinine clearance rate
Rate by which creatinine is cleared from blood
- an indicator of GFR
- causes of decrease: prerenal, renal, postrenal
74
Indications for creatinine clearance rate
- assess GFR in nonazotemic, non-dehydrated animals suspected of renal disease (usually polyuric)
- assess prognosis of azotemic animals
75
Creatinine clearance rate - endogenous procedure
Adequate hydration is confirmed, all urine produced during a given perion (20 min to 24 hrs)
- metabolism cage or catheterization
- record volume
- mixed well and creatinine is measured
76
Creatinine clearance rate - exogenous procedure
Same as endogenous, but creatinine is injected into the animal
- advantage: challenge to the kidney
- disadvantage: may increase tubular secretion of creatinine, lack of standardization
77
Urinalysis - physical exam
- color
- clarity
- USG
78
Urinalysis - chemical exam
Reagent strip method
- pH
- [protein]
- [glucose]
- [ketone]
- [heme]
- [occult blood]
- [bilirubin]
- [urobilinogen]
- sediment
79
Voided
Samples may have more bacteria, epithelial cells, and leukocytes from distal urethra and genital tract
80
Cystocentesis
Iatrogenic hemorrhage
81
Catheterized
Epithelial cells, hemorrhage, lubricant, bacteria
82
Off surface
Contaminated with a variety of microscopic material
83
Normal urine color
Amber
| - pale is less concentrated than dark yellow (not always)
84
Abnormal urine color
- red: erythrocytes
- red-brown: erythrocytes, hemoglobin, myoglobin, methemoglobin
- brown/black: methemoglobin (from hemo or myoglobin)
- yellow/orange: bilirubin
- yellow/brown or yellow/green: bilirubin or biliverdin
85
Horse urine may turn ____ when exposed to snow
Brown
| - non-pathogenic
86
Urine clarity
- clear-mild turbidity is normal (few epithelial cells, crystals)
- equine is usually turbid: mucoproteins and calcium carbonate crystals
- done in fresh, homogenized urine
- cloudiness: presence of cells, crystals, bacteria, casts, and lipid droplets
87
Solute concentration
Dissolved ions and molecules
| - Na, Cl, K, Ca, PO4, NH4, urea, creatinine
88
Specific gravity
Rate of solution weight/water weight
89
Refractive index
Ratio of the speed of light in the vacuum/speed of light in a solution
- increases proportionally to solute concentration
- correlates with osmolality
- suspended particles do not affect meaurement, may make it harder to read refractometer
- marked proteinuria or glucosuria may hyperestimate [solutes]
90
Is 1.060 the same in the dog and cat?
No, type of molecules are different
91
Freezing point osmometry method
Freezing point of a solution is inversely related on the concentration of solutes
- as the concentration increases, freezing-point decreases
- unit: mol/kg or osmol/kg
92
A lower USG is a worse prognosis until _____
Hyposthenuria
| - shows there is not a loss of nephron function, is related to ADH function
93
Carnivores have ___ urine and herbivores have ____ urine (unless they are on a milk diet)
Acidic; alkaline
- dogs and cats: 6-7.5 pH
- horses and cows: 7.5-8.5
94
Aciduria
Suggests increased secretion of H
- acidosis, respiratory and some metabolic
- hypochloremic metabolic alkalosis
- hypokalemia: secretion of H increases absorption of K
- furosamide treatment
- proximal renal tubule aciduria (if HCO3 is depleted)
95
Alkalinuria
Decreased excretion of H
- urea splitting hydrolysis: spontaneous delayed urinalysis completion, urease containing bacteria
- respiratory alkalosis
- distal renal tubular acidosis
- proximal renal tubular acidosis (without HCO3 is depletion)
96
Proteinuria - physiologic
Proteins <68 kD may pass glomerulus
- usually resorbed, may be in urine
- dogs have measurable amount of low protein (mostly albumin)
- Tamm-Horsfall protein --> hyaline cast formation (soluble on pH >7)
97
Proteinuria detection
- strips: detect albumin better than globulins
- SSA: denaturation of proteins by acids forming precipitation (turbid urine)
- may help to access some types of proteinuria
98
Tamm-Horsfall protein is secreted by ____
Tubules!
99
Prerenal proteinuria
- overflow, overload, and preglomerular
- increased concentration of small proteins
- paraproteinuria (light chain proteins --> Bense Jones)
- hemoglobinuria
- myoglobinuria
- postcolostral proteinuria
100
Glomerular proteinuria
Damage to glomeruli will allow larger proteins to pass
| - usually negatively charged, selective protein loss
101
Tubular proteinuria
Proximal tubules are not resorbing proteins
| - usually acute renal disease, can be congenital
102
Hemorrhagic or inflammatory proteinuria
Exudation of proteins through increased permeability of vessels
- postrenal (more common)
- usually see pyuria or hematuria
103
Glucose
180mw, resorbed in proximal tubules by Na/glucose cotransport
104
Max glucose transport ability
- dogs: 180-220 mg/dL
- cats: 290 mg/dL
- horses and calves: 150 mg/dL (probably lower in mature cattle)
105
Glucose analytical methods
- strip: false neg with ascorbic acid, ketonuria, very concentrated urine
- copper reduction method: may be used to confirm
106
Hyperglycemia
More glucose in ultrafiltrate that can be resorbed
| - usually will see hyperglycemia but a transient hyperglycemia with a delay to empty the bladder may mask
107
Renal glucosuria
Normoglycemic
- tubular abnormalities: acquired or congenital
- acquired: renal tubular toxicosis or ischemia
- congenital: fanconi syndrome and pure primary renal glucosuria (basenji, norwegian elkhound, shetland sheepdog)
108
Glucosuria will cause
- osmotic diruesis
- decreased concentration ability
- increased urine volume
109
Ketones
Acetoacetate, B-hydroxybutyrate, acetone
- not expected in urine of healthy animals
- may enter thru glomerular filtration or secretion by tubular cells
110
Ketones - analytical method
- strip: false positive with pigmented urine and other compounds
- only high concentrations of B-hydroxybutyrate
- acetest table method: blood, plasma, urine, milk
111
Ketonuria
Increased metabolism of lipids
- decreased insulin and increased glucagon
- may lead to Na and K depletion
112
Heme - strip test
Could be hemoglobin, myoglobin, methemoglobin
| - intact cells are lysed in the reagent pad
113
Heme - hematest tablet test
Confirmatory
| - occult blood in feces
114
Heme - heme positive
Hematuria
- hemorrhage in the urinary tract
- RBCs may lyse if USG is <1.015
115
Hemoglobinuria
Intravascular hemolysis after haptoglobin is saturated
| - RBCs may lyse if USG is <1.015
116
Myoglobinuria
Myocyte damage or necrosis (rhabdomyolysis)
117
Methemoglobin
Oxidation of hemoglobin iron in the urine
| - oxidative damage causing intravascular hemolysis
118
Bilirubin
Not expected in normal urine of mammals other than the dog
- conjugated bilirubin pass freely thru glomeruli
- heme converted into unconjugated and then conjugated bilirubin by renal tubular cells
- strip or ictotest
119
Bilirubinuria
Hemolytic states or decreased excretion of bilirubin
- concentrated urine from healthy dogs frequently produces small bilirubin reaction
- may be present before hyperbilirubinemia or icterus are detected
120
Urobilinogen
- colorless
- from degradation of bilirubin in intestine
- excreted by urine, o removed by hepatocytes
- reagent strip
121
Increased urobilinogenuria
Hemolytic states or hepatobiliary disease
| - not clinically relevant
122
Nitrite
Gram-neg bacteria reduce nitrate to nitrite
- strip: false positive with contaminant bacteria
- positive reaction: presence of gram neg bacteria, significant bacteriuria
- not clincially relavent due to inconsistency of results
123
Leukocyte esterase
Leukocyte in the urine release esterase
| - false negative in dogs and false positive results in cats
124
Urine sediments
Consistently using the same volume allows a more accurate/clinically relevant semiquantitative result
- contents not stable, so use fresh urine
- cells and casts deteriorate
- crystals can form or dissolve
- bacteria may die or proliferate
- mix well before aliquot is removed for centrifugation
- most sediment findings quantified based on number seen per hpf
- staining sediments done, but dilution should be taken into account
125
Leukocytes
Few is found in healthy animals
| - less than 5/hpf
126
Pyruia
Increased leukocytes/hpf
- inflammation of mucosal or submucosal tissues or renal parenchyma
- infectious or noninfectious
- knowledge of collection may determine site of inflammation
- genital tract inflammation
127
Hematuria
- pathological hemorrhage: vascular damage, thrombocytopenia, thrombopathia, vWD, coagulopathies
- iatrogenic hemorrhage: cystocentesis, catheterization
- urogenital tract: estrus
128
Urine should be ______
Sterile
129
Bacteruria
Semiquantified, may proliferate after collection
- stained air-dried slides to increase accuracy
- source of sample, presence/absence of pyruia, concentration of bacteria
- false neg --> urine culture recommended
130
Casts
Cylindrical concretions: shape mirrors tubular segment
- matrix of Tamm-Horsfall mucoprotein and other
- casts may form from normal sloughing of tubular cells (hyaline or granular): <2/lpf
- may deteriorate (in alkaline urine)
131
Cylindruria
- hyaline: healthy animals, glomerular proteinuria
- epithelial or fatty: active tubular degeneration or necrosis
- granular: tubular degeneration, necrosis or inflammation, healthy animals
132
Epithelial cells
From urinary tract mucosa
- renal tubular, transitional cells, squamous epithelial
- presesnt in ehalthy animala
- inflammation can increase release
- neoplastic cells may be present
133
Crystals
Precipitation of salts
| - pH may dictate formation or dissolution of crystals
134
Crystalluria
Found in healthy animals, increased concentration may suggest presence of some pathological state
- presence/absence of crystals is not a reliable indicator of presence/absence of uroliths
- crystalluria is a risk factor for urolith formation
135
Calcium oxalate dihydrate and monohydrate
Envelope shape
- healthy dogs and cats
- calcium oxalate uroliths
136
Dogs intoxicated with ethylene glycol more commonly have _______
Calcium oxalate monohydrate
137
Calcium phosphate
- healthy dogs
- peristent alkaline urine
- calcium phosphate urolith
- infection induced struvite crystalluria
138
Cholesterol
- healthy dogs
| - in humnas with excessive tissue destruction, nephrotic syndrome and chyluria
139
Cystine
- hexagonal
- concentrated acidic urine
- alkaline urine due to infection or contamination with urease-producing bacteria may cuase the crystal to dissolve
- dogs and cats with cystinuria (autosome recessive disease)
140
Magnesium ammonium phosphate
Struvite
- coffin
- normal dogs and cats
- infection with urease-producing bacteria
- sterile struvite uroliths
141
Urate
Yellow to brown spherules with long irregular protrusions
- dogs with partial vascular anomalies
- dogs and cats with ammonium urate uroliths
- uncommon in healthy dogs/cats
142
Bilirubin
- needle like
- yellow to brown
- concentrated urines
- healthy dogs
- cholestatic disease in cats, horses, bovine, camelids
143
Calcium carbonate
Not described in dogs and cats, healthy in horses and goats
144
Organisms other than bacteria
Yeasts, hyphal structures, algae and parasitic structures
| - parasitical structures may be due to fecal contamination
145
Lipid droplets
Likely from renal tubular epithelium
- most common in cats (store TG in renal tubular cells)
- use of lubricants for catheterization
146
Mucous strands
```
Urogenital secretions (abundant in horses)
- spermatozoa: expected in intact males, occasionally in females after breeding
```
