urinary system notes pt 6

Question 1

renal tubules function

Answer 1

• selective resorption of the vast majority of the plasma ultrafiltrate
• 99 % of filtered water and sodium is reabsorbed
• wastes are excluded and pass through the collecting ducts to the lower urinary tract

Question 2

proximal convoluted tubule - cellular structure and function

Answer 2

• The proximal convoluted tubular epithelial cells have a prominent brush border and large numbers of mitochondria
  > related to their involvement in active (requires energy) resorption of sodium and chloride as well as ~90 % of hydrogen excretion
• Water is resorbed isotonically following the sodium chloride gradient
• Along with sodium, amino acids, glucose, calcium, phosphate, uric acid, small proteins, and potassium are reabsorbed
• sodium bicarbonate moves with the hydrogen ions
  <><><><>
• To facilitate this massive movement of molecules, the proximal convoluted tubules are in close apposition with the peritubular capillaries

Question 3

summary of molecule movements to / from the proximal convoluted tubule

Answer 3

Reabsorbed:
- Na, Cl, water
- Amino acids
- glucose
- Ca
- phosphate
- uric acid
- small proteins
- K
<><><><>
Excreted:
- H+, NaHCO3
> (hydrogen ions, sodium bicarbonate)

Question 4

loops of Henle, structure and function

Answer 4

composed of a descending loop followed by an ascending loop
<><><>
- ascending loop actively pumps NaCl into interstitium
> draws water out of the descending loop
- (the medulla is the only hypertonic tissue under normal conditions)
- ascending loop is impermeable to water, so fluid does not get pulled back into the ascending loop
<><><>
- Mg and Ca are also reabsorbed in the loop of Henle

Question 5

distal convoluted tubule - what does it do?

Answer 5

• pumps out NaCl, water molecules follow

Question 6

collecting ducts and tubules - what is reabsorbed?

Answer 6

• water is reabsorbed

Question 7

Tubular disease usually manifests how?

Answer 7

• changes to the tubular epithelial cells
• hydropic degeneration, tubular necrosis, hyaline droplets, fatty degeneration, and thickening of the tubular basement membrane all possible

Question 8

acute tubular degeneration and necrosis - usual origins
- features
- lesions, progression

Answer 8

• usually metabolic, ischemic, or toxic
• distribution of lesions is usually diffuse and cortical, with swelling, pallor, and a wet appearance being the initial changes
• In their extreme form, the kidneys will be wet with a large amount of perirenal edema, and they will be a pale- tan colour

Question 9

Ischemic acute tubular necrosis
- when is this usually seen?
- hostological lesions
- causes? how common?

Answer 9

• most often is seen following hypotension that results in severe renal ischemia
• characteristic histological lesion is patchy focal necrosis along nephrons, especially in the proximal tubules, less so in the distal tubules
• with more severe lesions there is tubulorrhexis (disruption of the tubular basement membranes) with variable occlusion of tubular lumens by casts
• Glomeruli are usually normal
• interstitial changes include edema and leukocyte infiltration
  <><><><><>
  Anoxic/ischemic disease is relatively common in companion animals
• Dehydration, reduced cardiac output, reduced respiration while under anaesthesia, and diseases with anemia or hypoxemia can all cause renal cortical tubular degeneration and necrosis

Question 10

Nephrotoxic acute tubular necrosis
- how it occurs?
- what structures are affected?
- agents

Answer 10

• exogenous toxins
• extensive necrosis predominantly affecting the proximal tubules
  > may have preserved basement membrane
  <><>
• Proximal tubules are particularly susceptible to toxins because they have a high level of metabolic activity and they are exposed to the toxic agents via the large volume of glomerular ultrafiltrate they are involved in resorbing
  <><><><>
• generally rare
• Ethylene glycol toxicosis most common
• others include: heavy metals, antibacterial and antifungal agents, NSAIDs, plants, oxalates, mycotoxins, antineoplastic compounds

Question 11

Ethylene glycol
- why is it ingested
- cats vs dogs
- disease progression
- clinical signs

Answer 11

• voluntarily ingested due to sweet taste
• cats have lower minimal lethal dose than dogs
• metabolites are primary nephrotoxins that deplete ATP levels and destroy membrane phospholipids and some enzyme activity
  <><><>
• Acute: depression and ataxia with osmotic diuresis
• Central nervous signs are due to aldehydes present and possibly due to the severe metabolic acidosis
• Over the proceeding 12 hours cardiovascular and respiratory signs develop including pulmonary edema, tachypnea, and tachycardia
• If the animal survives the initial disease, renal failure develops around day 1-3
• Renal failure develops largely due to nephrotoxicity in the tubules
• calcium oxalate crystals form in tubular lumens, tubular epithelial cells, and in the interstitium
  > The crystals are thought to contribute to the development of renal failure
  <><><><>
• lesions most severe in proximal convoluted tubules

Question 12

survivors of ethylene glycol toxicosis will deal with what issues?

Answer 12

• chronic disease involves the non-specific lesions of renal fibrosis, with crystals disappearing over time

Question 13

Oxalate toxicosis
- what animals? why?
- effects on the body and kidneys

Answer 13

• most common in cattle and sheep, where ingested plants usually are the source of the oxalate
  > consumed when lack of alternative food sources are available
• sporadic fatalities, mostly sheep
  <><><><>
• Calcium oxalate precipitates in vessel lumens and/or walls causing hypocalcemia as well as vascular necrosis and hemorrhage
  > crystals cause tubular obstruction and can lead to acute renal failure
• oxalates may also impair oxidative phosphorylation by chelating intracellular calcium and magnesium
• Oxalates can also cause an acute gastroenteritis with high enough levels of consumption
• chronic exposure can lead to fibrous osteodystrophy

Question 14

Aminoglycosides
- effects on kidneys
- which are most toxic?
- signs
- long term effects? reversible?

Answer 14

• obligate nephrotoxins
  > neomycin, kanamycin, and gentamycin are the most toxic
• eliminated from the body by glomerular filtration and accumulate in proximal tubules where they cause damage and necrosis
  <><><><>
• impair ability to concentrate urine
• polyuria, enzymuria, proteinuria, hematuria, and azotemia
  <><><>
• Aminoglycoside toxicity is reversible and regenerating cells actually have increased resistance to the toxic effects of aminoglycosides
• However, progression to acute renal failure does occur.

Question 15

Tetracyclines - effects on kidneys? species?

Answer 15

• can cause acute tubular necrosis and renal failure, having been reported in dogs and young and old cattle
  > New versions such as doxycycline have not been reported to be nephrotoxic

Question 16

Sulfonamide toxicity - effects on kidneys

Answer 16

• much rarer with newer shorter-acting sulphonamides
• lesions are due to both local toxic effects and due to tubular obstruction by the sulphonamide crystals that form

Question 17

Amphotericin B - effects on kidneys

Answer 17

leads to renal dysfunction because it is both directly toxic to tubular epithelium and causes renal vasoconstriction leading to diminished renal perfusion which results in decreased glomerular filtration

Question 18

Hemoglobinuric/myoglobinuric acute tubular necrosis
- disease where this occurs in sheep, dog, and horse

Answer 18

• Copper toxicosis (sheep)
• immune hemolytic anemia (dog)
• rhabdomyolysis (horse)
  <><><>
• hypoxic/anemic and prerenal causes are probably involved

Question 19

unifying histologic lesions of tubulointerstitial diseases

Answer 19

• tubules and interstitium are intimately linked both anatomically and functionally and diseases of one ultimately involve the other
• degeneration of the tubules and inflammation and fibrosis in the interstitium

Question 20

glomerular disease vs tubular disease main clinical signs / observations

Answer 20

• glomerular disease is usually manifested clinically as persistent proteinuria
• animals with tubular disease tend to have problems concentrating urine and/or with resorption of specific molecules

Question 21

Interstitial nephritis
- what characterizes it?
- when should we consider it?
- gross appearance?
- causes in various species
- acute presentation
- chronic presentation

Answer 21

• characterized by inflammatory infiltrates that vary depending on the cause
• Only consider interstitial nephritis once embolic and pyelonephritis have been excluded
• multifocal and coalescing, with white foci present throughout the kidney
  <><><><>
• leptospirosis (dogs, cattle pigs)
• white spotted kidney (E. coli in calves – a multifocal nonsuppurative interstitial nephritis)
• equine viral arteritis
• PRRS
  <><><><>
• mostly subclinical
• Acutely: interstitial edema, infiltration of leukocytes and focal necrosis of renal tubules
• Chronic: interstitial fibrosis, leukocytic infiltrate becoming almost exclusively mononuclear and widespread tubular atrophy apparent

Question 22

Embolic suppurative nephritis
- nature of the disease
- cause, distribution
- lesions

Answer 22

• both a glomerular (sometimes causing acute suppurative glomerulitis) and tubular disease
• result of bacterial infection that has spread hematogenously > multifocal
• Small bacterial emboli localize to glomeruli and/or peritubular capillaries and cause single to multiple small to large abscesses
• Larger emboli can cause septic infarcts with parenchymal necrosis and abscess formation

Question 23

Granulomatous/pyogranulomatous nephritis
- classic disease
- lesions
- other diseases

Answer 23

• classic pyogranulomatous disease is feline infectious peritonitis caused by feline coronavirus
• lesions tend to follow blood vessels and a fibrinoid vasculitis is the hallmark lesion
  <><><>
• Migrating ascarid larvae in dogs is another cause
• hairy vetch toxicosis (Vicia villosa) causes a multisystemic granulomatous disease that involves the kidneys in cattle (mostly cortex)

Question 24

pyelonephritis
- ascending vs descending
- sex
- lesions

Answer 24

• usually bacteria ascending from bladder
• can also be ‘descending’ i.e. from the blood
  <><><>
• female > male
• segmental lesions, extend from pelvis to capsule
• pelvis and ureters are inflamed, and the papillae and medulla are affected and often necrotic or eroded, especially at the renal poles
• White or hemorrhagic bands extend to the capsular surface
• chronic forms have segmental fibrosis, esp cats
• pyonephrosis
• perinephric abscesses can develop

Question 25

pyonephrosis - definition

Answer 25

- indicates there is severe renal suppuration in combination with complete, or nearly complete, obstruction of the ureter, resulting in the kidney eventually becoming a bag of pus

Question 26

common agents of pyelonephritis

Answer 26

- usually endogenous and are part of the rectal flora or are opportunists found normally on the skin <><><><> - E. coli and other enterobacteriacae (all species, cats especially) - Corynebacterium renale (cows, contagious bovine pyelonephritis) - Actinobaculum (Eubacterium) suis (sows, porcine contagious pyelonephritis)

Question 27

hypercalcemic nephropathy - species - causes - mechanism - lesions

Answer 27

- cats and dogs > hypercalcemia of malignancy or with pseudohyperparathyroidism > less commonly vitamin D containing rodenticides and primary hyperparathyroidism, or ingestion by grazing animals of plants containing vitamin D3 <><><><> - calcium inactivates adenyl cyclase > interferes with sodium transportation in nephron - Ca also interferes with antidiuretic hormone receptors in the collecting duct <><><> - can lead to progressive renal mineralization that starts in the tubular basement membrane and epithelial cells and progresses to involve the interstitium, blood vessels, and glomeruli > lesions most prominent in the outer medulla

Question 28

Acute renal failure typically presents with:

Answer 28

- rapid onset of oliguria/anuria and azotemia

Question 29

Uremia definition:

Answer 29

technically means urine in the blood however the term is most often used to describe the clinical syndrome of renal failure.

Question 30

To get to uremia, there are four stages based on the amount of glomerular filtration rate remaining:

Answer 30

1. Diminished renal reserve – GFR ~ 50% of normal – no apparent disease 2. Renal insufficiency – GFR 25-50% of normal – azotemia, polyuria 3. Renal failure – GFR 20-25% of normal – homeostasis lost, uremia 4. End-stage renal disease – GFR <5% of normal

Question 31

uremia - how does it arise - what is it? - outcomes?

Answer 31

- failure of the function of the kidneys results in a multisystemic syndrome known as uremia > includes azotemia and the systemic effects of renal failure <><><><><><> - There are both renal and nonrenal lesions in uremia - Death is often because of metabolic abnormalities such as hyperkalemia, metabolic acidosis, and pulmonary edema

Question 32

are uremic animals always azotemic?

Answer 32

uremic animals are always azotemic, azotemic animals are not always uremic

Question 33

nonrenal lesions associated with chronic renal failure

Answer 33

* uremic glossitis (oral ulcers and necrotic stomatitis). * uremic gastropathy (ulcerative and hemorrhagic a/o necrotic gastritis). Horses and cattle get ulcerative and hemorrhagic colitis. * uremic pneumonopathy (pulmonary edema and mineralization) * pulmonary, atrial, and aortic thrombosis * fibrinous pericarditis * tissue mineralization in other locations (more common in dogs) – pericardium, soft tissues, arteries * poorly responsive/hypoplastic anemia * parathyroid hyperplasia * fibrous osteodystrophy <><><><><><><> The places to look for lesions therefore include the kidney, tongue (ulcers), jaw (rubber jaw) and ribs, parathyroid (hyperplasia), intercostal spaces (mineral), lungs (edema, mineral), heart and great vessels (mineral, thrombosis), and stomach/intestinal tract (hemorrhage, mineralization).

Question 34

pathogenesis of uremia - basic cause for each lesion is related to either:

Answer 34

basic cause for each lesion is related to either: - vascular changes (altered permeability and/or endothelial degeneration and necrosis) - alteration of acid base and calcium balance - secondary hyperparathyroidism - direct injury by ammonia

Question 35

sublingual ulcers with uremia - cause

Answer 35

result from either: - a local vasculopathy > and/or - direct toxicosis of ammonia produced by local bacteria who convert urea that is excreted in large amounts in the saliva > can also have uremic gingivitis and an ammonia smell to the animal’s breath

Question 36

Uremic gastritis with uremia is a result of:

Answer 36

- mineralization and vasculopathy with ischemia <><><><> Grossly: - large areas of swollen gastric mucosa full of dark red to black blood with occasional ulcerations - In large animals: often colitis with mild edema observed in the stomach and upper intestines <><><><> Histologically: - ulceration and necrosis and (uniquely) mineralization in the middle and deep zones of the mucosa

Question 37

Uremic pneumonopathy cause

Answer 37

- due to increased permeability of vessels because of a direct degenerative effect on the alveolar capillaries (vasculitis) as well as mineralization

Question 38

Metastatic mineralization with uremia - what is it / when does it occur - appearance

Answer 38

- occurs when ionized calcium and phosphorus precipitate, partly in tissues with an alkaline pH - The classic example is the appearance of lines of mineralization (“ladder-like”) of the subpleural connective tissue, particularly in the cranial intercostal spaces <><><><> Develops due to: - hypercalcemia from reduced renal loss from decreased GFR - reduced parathormone degradation in the kidney - increased organic cations that complex calcium - exaggerated response to Vitamin D - autonomous PTH secretion (is chronic renal dialysis patients)

Question 39

Fibrous osteodystrophy occurs due to

Answer 39

hyperparathyroidism

Question 40

Thrombosis with uremia - why does it occur? - common place

Answer 40

- due to damage to endothelium, and, in severe protein losing disease (nephrotic syndrome) to the loss of antithrombin III and plasminogen activators in the urine - Thrombosis of the renal vein

Question 41

lesions of chronic uremia

Answer 41

fibrosis, mineralization, and glomerular sclerosis, sometimes with focal areas of tubular hyperplasia/hypertrophy, commonly occur.