Urinary System Pathology

Question 1

3 main functions of kidneys.

Answer 1

Homeostasis.
- acid-base balance.
- water and electrolyte balance.
Formation of urine.
- elimination of metabolic waste.
Endocrine:
- RAAS.
- erythropoietin.
- vit D activation.

Question 2

1. Normal kidney appearance in some cats - why?
2. What do pigs have rather than a renal crest?
3. What do bovine kidneys have instead of renal pelvis?

Answer 2

1. Pale tan-cream cortex - fat storage.
2. Renal papillae.
3. Ureter passes through renal hilus, branches and forms a funnel-shaped calyx around each of the renal papillae.
   * they have lobular kidneys.

Question 3

Structural components of the kidney.

Answer 3

Vasculature.
Glomeruli.
Interstitium.
Tubules.
These are interdependent and irreversible damage to one component will result in impaired function of other components.

Question 4

Renal vasculature.

Answer 4

Renal artery enters, branches to interlobar arteries, branch to arcuate arteries (on corticomedullary junction), interlobular arteries (in cortex) branch from arcuate arteries.
* arcuate arteries do not anastomose.

Question 5

What further vasculature in the cortex comes from the interlobular arteries?

Answer 5

Afferent glomerular arteriole to
glomerular capillaries to
efferent glomerular arteriole.

Question 6

What follows the efferent glomerular arteriole?

Answer 6

Peritubular capillaries and vasa recta that surround loop of Henle and convoluted tubules.

Question 7

What would happen to tubules if there was a decreased peritubular perfusion caused by glomerular disease?

Answer 7

Tubular atrophy.

Question 8

1. What surrounds the glomerulus?
2. What is the collective name for the glomerulus and this other structure?
3. What is the function of the glomerulus?

Answer 8

1. Bowman’s capsule.
2. Renal corpuscle.
3. To filter blood.
   - 3 layers of the glomerular filtration barrier:
   – endothelium lining blood vessels –> much leakier than endothelium in most other parts of the body.
   – glomerular basement membrane.
   –> made up of network of collagen and other bits of matrix, is charged so is permeable to water and small solutes and small proteins, but not large proteins.
   – podocytes.
   –> cells that interdigitate with little foot processes, creating slits and dictating size of anything that comes through the filter.

Question 9

If injury to the glomerular filtration barrier causes increased permeability, what plasma component is most likely to start to appear in the urine?

Answer 9

Proteins - proteinuria.

Question 10

Tubules in the kidney.

Answer 10

Proximal convoluted tubule.
- a lot of resorption of fluids and salts (passive).
Loop of Henle.
- water absorption and sets up hypertonicity within the medulla.
Distal convoluted tubule.
Collecting duct.
- ADH acts to determine whether or not it allows water to re-absorbed from these tubules.

Question 11

Function of tubules.

Answer 11

Reabsorption of components of the glomerular filtrate.
- tubular system can re-absorb up to 99% of the water in the glomerular filtrate.
- requires energy e.g. Na pumps.
- active transport may become saturated e.g. glucose reabsorption.
Excretion of substances.
- e.g. H+ and bicarbonate for acid-base regulation.
Functions require close apposition of tubules and peritubular capillaries.
- disruption of this relationship will affect tubular function.

Question 12

Normal interstitium.

Answer 12

ECM, cells and fluid within the space between renal tubules, renal corpuscles and vasculature.
Normally relatively sparse.

Question 13

Interstitium pathology consequences.

Answer 13

Interstitial expansion.
- e.g. fluid entry e.g. oedema, haemorrhage.
- e.g. cell entry e.g. inflammatory, neoplastic.
- e.g. connective tissue e.g. collagen.
- e.g. other substances e.g. calcium, amyloid.
This can interfere with relationship between the tubule and blood vessels, affecting the functioning of the kidney.

Question 14

Routes of entry of aetiological agents to the urinary tract?

Answer 14

Haematogenous into tissues.
Via glomerular filtrate/urine:
- entering as it travels through the urinary tract – can then contact luminal surface of tubules, ureters, bladder or urethra.
Ascending infection - from externally via urethral entrance or from a site of infection within the urinary tract.
Direct penetrating injury e.g. cystocentesis.

Question 15

1. Causes of renal vascular injury?
2. Manifestations of renal vascular disease/injury?

Answer 15

1. Obstruction - embolism, thrombosis.
   Vascular injury and inflammation (vasculitis).
   Compression of blood vessels. ‘
   Loss of autoregulation of renal perfusion.
2. Ischaemia, infarctions, necrosis, atrophy.
   Haemorrhages.
   Inflammation.

Question 16

(Thrombo)embolism and infarction in the kidney.

Answer 16

Interlobar or smaller vessel infarction most commonly.
- Causes localised infarction of a segment of the cortex.
Arcuate vessels or interlobar less commonly.
- Causes localised infarction of a segment of cortex and medulla.
Renal artery uncommonly.
- Causes total or subtotal infarction of the kidney.

Question 17

Process of infarction in the kidney from acute to chronic.

Answer 17

Acutely, swelling and blackened tissue. Whole kidney darker red. Lots of blood in infarction.
After a few days, gets paler as blood pushed out and blood starts to haemolyse and break down and haemoglobin diffuses out. Still swelling.
Subacutely, swelling goes, inflammation and redness of viable tissue around infarction.
Chronically, indentation as all necrotic tissue has been removed by phagocytosis, left scarring and whitened tissue.

Question 18

2 cardiac diseases that may cause secondary renal infarction.

Answer 18

Hypertrophic cardiomyopathy (HCM) (usually sterile).
- thrombi formation in the atrium.
– thromboemboli break off and can lodge in kidney.
Endocarditis affecting the mitral valve and/or aortic valve.
(septic thromboembolism).

Question 19

Causes of vasculitis?

Answer 19

Thromboembolism - sterile or septic.
Bacteraemia, viraemia.
FIP.
- vasculitis and multifocal pyogranulomatous nephritis
Can lead to formation of micro-abscesses at glomeruli and other sites.
Can spread throughout kidney.
Pattern can look similar to an ascending infection.
Diseases:
- Porcine Erysipelas infection.
– renal haemorrhage can also occur.
- African Swine Fever (notifiable).
– haemorrhage can also occur here.
- Canine Herpesvirus infection.
– Also haemorrhages here, and necrosis.

Question 20

Compression of blood vessels in the kidney.

Answer 20

Hydronephrosis and hydroureter secondary to impaired urinary flow resulting from downstream obstructive disease.
- leading to atrophy and loss of tissue.

Question 21

Loss of autoregulation of renal perfusion.

Answer 21

Normally, renal hypotension leads to ischaemia leads to prostaglandin production in the medulla leads to vasodilation of afferent arterioles in juxtamedullary nephrons which helps to maintain perfusion of the inner cortex and medulla.

Interruption of this e.g. by administering NSAID which interferes with prostaglandin production in medulla, so afferent arterioles do not dilate and perfusion of inner cortex and medulla are not maintained which means may result in medullary necrosis.

Question 22

Causes of renal medullary (papillary) necrosis or atrophy?

Answer 22

Compression of vasculature:
- urinary obstruction.
- medullary amyloidosis (uncommon).
Loss of autoregulation of renal perfusion.
Pyelonephritis.

Question 23

Potential functional effects of glomerular injury.

Answer 23

Damage to barrier could cause proteinuria and PLN.
Impaired glomerular blood flow could cause impaired ultrafiltrate formation, impaired peritubular perfusion which causes reduced nephron function.
Severe or persistent injury can cause glomerular tuft atrophy or sclerosis which causes a loss of nephron function.

Question 24

Causes of glomerular injury.

Answer 24

Entrapment of thromboemboli.
Infectious agents.
Deposition of substances in glomeruli e.g. immune complexes, amyloid.
Chronic glomerular changes can also result from conditions affecting glomerular blood flow or tubular funnction.

Question 25

1. Define glomerulitis.
2. Define glomerulonephritis.
3. Define glomerulopathy.

Answer 25

1. Inflammation restricted to glomeruli.
2. Implies primary glomerular disease and secondary changes in other components of the nephron e.g. tubulo-interstitial, vasculature.
3. Glomerular disease without inflammation or with an uncertain aetiopathogenesis.

Question 26

Suppurative glomerulitis (embolic nephritis).

Answer 26

Bacteraemia with bacteria lodging in glomerular capillaries +/- interstitial capillaries.
- causes formation of micro-abscesses.

Question 27

Glomerulonephritis.
Causes and pathological effects.

Answer 27

Caused by mostly glomerular deposition of immune complexes (immunoglobulins and/or complement components).
Can cause changes in the basement membrane.
- proliferation of glomerular cells (mesangial and/or endothelial) (proliferative).
- inflammatory cell infiltrates (membranoproliferative).
- expansion and damage so increase permeability (membranous).
Often secondary to infectious agents or neoplastic diseases.
- need to establish underlying cause.
Not hugely common.
Can be very serious when does occur.

Question 28

Glomerulonephritis consequences.

Answer 28

Damage to glomerular filtration barrier (increased permeability).
Proteinuria.
- damage to tubular epithelial cells.
Interstitial fibrosis.
Reduced nephron function.

Question 29

Gross appearance of glomerulonephritis.

Answer 29

Can appear normal.
Mottled or granular or stippled.
Can be difficult to identify grossly.

Question 30

Glomerular amyloidosis.

Answer 30

May be associated with chronic inflammatory diseases or neoplastic diseases.
Renal amyloid deposition most commonly affects glomeruli and can cause progressive proteinuria and renal insufficiency.
Less commonly, deposited in renal medulla, esp. in cats and Shar-pei dogs.

Question 31

Causes of tubular damage.

Answer 31

Nephrotoxins.
- NSAIDs, aminoglycosides, tetracyclines, sulphonamides, cisplatin.
- heavy metals.
- oxalates – antifreeze (ethylene glycol).
- microorganism/plant toxins
– bacterial, fungal, oak, raisins/grapes (dogs), lilies (cats).
- pigments – haemoglobin, myoglobin.
- hypercalcaemia.
Ischaemia.
Infectious agents.

Question 32

Tubular epithelial responses to injury.

Answer 32

Atrophy.
Degeneration.
Necrosis/apoptosis.
Regeneration - of lining of tubules.
Inflammatory disease involving tubules often causes “tubulointerstitial nephritis”.

Question 33

1. Acute tubular degeneration and necrosis causes and cause of.
   - histo?
2. Functional consequences of acute tubular degeneration and necrosis.

Answer 33

1. Important cause of AKI.
   Most common causes are nephrotoxic injury and ischaemia.
   - Get necrotic tubular epithelium.
   - Get inflammatory cells in the interstitium.
2. Intratubular obstruction by sloughed necrotic epithelium.
   Increased tubular permeability allows leakage of filtrate out of the tubules and absorption back into blood.
   Vasoconstriction from tubuloglomerular feedback mechanisms.
   Get oliguria or anuria (decrease or absence of urine production).

Question 34

Ethylene glycol (antifreeze) poisoning.

Answer 34

Minimal lethal dose:
- 1.5ml/kg cats.
- 6.6ml/kg dogs.
Some ethylene glycol excreted unchanged, some metabolised to other metabolites incl. lactic acid, and oxalate.
- acute tubular injury.
- oxalate crystals precipitate in tubules and cause tubular obstruction.
See oxalate crystals on microscopy.
Grossly, difficult to determine.

Question 35

Can the tubules regenerate following tubular degeneration and necrosis?

Answer 35

If basement membrane intact, surviving epithelial cells can proliferate and regenerate and spread across basement membrane to eventually repopulate the tubule with epithelium.
Have limited functional capability during regeneration period as cells are immature e.g. limited reabsorption so polyuria.
Can take 3-8w for full function to return.

If basement membrane disrupted (tubulorrhexis), sloughing of necrotic cells and activation of macrophages and fibroblasts, preventing normal restoration of tubule.
Get fibrosis and tubular atrophy, some imperfect tubular regeneration.

Question 36

Copper toxicity in the kidneys of sheep.

Answer 36

Copper accumulation in the liver.
Can overwhelm capacity of liver to retain it.
- necrosis of hepatocytes, release of copper into blood, causing acute haemolytic crisis (hypoxia), haemoglobin filtered into kidneys, bringing about dark red, blackish kidney appearance and kidney damage..
Haemoglobin and myoglobin can be nephrotoxins.

Question 37

1. Interstitial injury in the kidneys.
2. Interstitial injury causes and responses.

Answer 37

1. Usually occurs in conjunction with injury to glomeruli, tubules (tubulointerstitial nephritis) and vascular components of kidney.
2. Toxins.
   Infectious agents - various routes of entry.
   - e.g. lepto, encephalitozoon cuniculi, malignant catarrhal fever, equine infectious anaemia, leishmania, FIP, haematogenous (embolic nephritis) or ascending (pyelonephritis) bacterial infections.
   Interstitial responses:
   - oedema.
   - inflammation.
   – acute or chronic.
   – localised or generalised.
   - fibrosis.

Question 38

Histological appearance of interstitial injury?

Answer 38

Inflammatory cell infiltrate +/- fibrosis (collagen).
Increased separation of the tubules caused by this.
- can lead to tubular atrophy.

Question 39

Interstitial nephritis.

Answer 39

Often a common final pathway of many kidney diseases, which leads to CKD, due to interdependence of components.
Appearance variable depending on degree and extent of fibrosis.

Question 40

Pyelonephritis.

Answer 40

Inflammation of renal pelvis and renal tubules causing tubulointerstitial nephritis.
Bacteria ascend from LUT infection.
- predisposing factors include conditions that encourage vesicoureteral reflux of urine from urinary bladder into ureters.
– e.g. stones, uroliths, cystitis.
Grossly, can be pustular, can ahve ascending infection areas that resemble infarcts.

Question 41

What is normal for horse kidneys.

Answer 41

Production of mucus in renal pelvis
Can resemble pus.

Question 42

Renal cysts.

Answer 42

Congenital or acquired.
Simple renal cysts:
- most common in pigs and calves.
- one or more cysts, unilateral or bilateral.
- usually incidental.
– usually unproblematic unless many of them.
Polycystic kidney disease (PKD):
- heritable in some breeds, sporadic in others.
- bull terrier.
- Persian cats: autosomal dominant (PKD-1 gene mutation).
– other mutations possible.
- progressive development of cysts may become clinically significant.

Question 43

Juvenile nephropathies.

Answer 43

Often familial/breed-related/hereditary conditions, mostly described in various breeds of dogs.
Chronic progressive renal disease in young dogs, resulting in renal failure (<1-2yrs).
Disorganisation in the kidney tissues (dysplasia).
Collagen-4 abnormalities affecting function, leading to glomerular disease.
Interstitial nephritis etc.
Quite uncommon.

Question 44

Ectopic ureters.

Answer 44

Ureter does not go into the trigone as it should.
- goes into neck, or urethra, or prostate, or vagina, or very rarely into the rectum.
Predisposes to ascending infection or obstruction, incontinence and constant dribbling of urine.

Question 45

Retrocaval/circumcaval ureter.

Answer 45

Ureter has an abnormal path.
Most commonly in cats.
Often incidental finding.
Can predispose to obstruction.
Developmental anomaly.
Can see secondary effects e.g. hydroureter.

Question 46

Cystitis.

Answer 46

Urinary bladder inflammation.
Can be sterile e.g. cats with FIC.
Often ascending bacterial infection.
Predisposing factors;
- female.
- local infections.
- obstructive urinary diseases / urinary stasis.
- trauma to bladder urothelium e.g. catheterisation, urolithiasis.
- DM – glucose encourages bacterial growth.
Can be acute or chronic.
- chronic – polyps of fibrous tissue and chronic inflammatory cells.
– dogs –> nodular proliferation of lymphoid tissue, may have concurrent urolithiasis (follicular cystitis).

Question 47

Renal neoplasia.

Answer 47

Primary renal tumours.
- epithelial most common – mostly renal carcinomas.
- others can include lymphoma, undifferentiated sarcomas, fibroma/fibrosarcoma, haemangioma / haemangiosarcoma, embryonal tumours (nephroblastoma).
- mets possible from kidney e.g. to brain, liver, lung, LNs etc.
Secondary renal tumours more common than primary.
Renal lymphoma in cats can be difficult to differentiate from other diseases and can present grossly in many different ways - nodular, diffuse.

Question 48

Urinary bladder neoplasia.

Answer 48

Primary neoplasia most common in dogs.
Epithelial (~90%).
- urothelial carcinoma (TCC) most common.
– often at bladder trigone.
– invasive and often metastasised by time of clinical diagnosis (~40%) to local LNs, lung etc.
- papilloma (may be multiple).
Others can include:
- leiomyoma/leiomyosarcoma.
- rhabdomyosarcoma in young dogs.