urinary system notes pt 5

Question 1

glomerulus primary function, structure
- how much filtration do they do per day?

Answer 1

• filter plasma
• composed of a capillary-rich mesenchymal mass with epithelium overlaying the capillaries (the visceral epithelium) and parietal epithelium lining the inner surface of Bowman’s capsule, which serves to collect the plasma ultrafiltrate
• Mesangial cells are found within the mesangial matrix that supports the glomerular capillary network. Derived from vascular smooth muscle cells, mesangial cells are both contractile and phagocytic
• Glomerular capillaries are fenestrated and negatively charged while the visceral epithelial cells (podocytes) have filtration slits
• These microanatomic features lead to selective permeability across the glomerular filtration membrane which, combined with high hydrostatic pressure in the renal arteriolar system results in a significant volume of glomerular ultrafiltrate, with the entire plasma volume being filtered approximately 100 times per day
• The podocyte filter slits and the fenestrations and negatively charged coating of the endothelial cells allow water and small molecules (sodium, urea, glucose, small proteins) to pass freely into Bowman’s space while higher molecular weight anionic plasma proteins such as albumin are, for the most part, retained

Question 2

glomerulus - what substances are filtered out of the plasma in the glomerulus? what is retained?

Answer 2

• water and small molecules (sodium, urea, glucose, small proteins) pass freely into Bowman’s space
• higher molecular weight anionic plasma proteins such as albumin are, for the most part, retained

Question 3

Terms used to specify the distribution/severity of glomerular disease:
- diffuse
- focal
- global
- segmental
- mesangial

Answer 3

• Diffuse – all/most of glomeruli affected to some degree
• Focal – only some glomeruli affected
• Global –the entire glomerulus is affected
• Segmental – only part of the glomerulus is affected
• Mesangial – disease primarily involves the mesangium

Question 4

In veterinary medicine, glomerular disease is generally classified into four broad groups, largely based on which component of the glomerulus is primarily affected and the lesions present.

• four classifications:

Answer 4

• Membranous – disease primarily involves thickening of the basement membrane
• Proliferative (mesangioproliferative) – disease primarily involves cellular proliferation
• Membranoproliferative – disease involves both thickening of the basement membrane and cellular proliferation
• Glomerulosclerosis – disease involves a combination of increased mesangial matrix, obliteration of the capillary lumens and progressive hyalinization/sclerosis

Question 5

what are mesangial cells?

Answer 5

• Mesangial cells are found within the mesangial matrix that supports the glomerular capillary network
• Derived from vascular smooth muscle cells, mesangial cells are both contractile and phagocytic

Question 6

Failure of function of the glomerulus occurs when:

Answer 6

• there is damage to the endothelium, basement membrane, or glomerular epithelium

Question 7

glomerular disease usually results in what sort of lesions? what is the outcome from a functional standpoint?

Answer 7

• Lesions are generalized and, because most are chronic, result in renal interstitial fibrosis
• Lesions can involve any combination of: cellular proliferation, leukocytic infiltration, thickening of basement membranes, hyalinization, and sclerosis
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• Regardless of the initiating injury, the glomerular filter is affected and larger molecules (particularly protein) pass through
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• Renal autoregulation of blood flow and obstruction of the glomerular capillary causes ischemia to the cortex
• cytokines from the glomerulus such as transforming growth factor (TGF)
  stimulate cortical fibrosis
• As all glomeruli are often affected, diffuse renal fibrosis develops, and this further affects renal function by reducing blood flow and nutrient transfer

Question 8

what proceeds clinical signs of glomerular disease, and is often a major part of the clinical picture?

Answer 8

proteinuria

Question 9

Generalized glomerulonephritis
- There are three main pathogenetic mechanisms that give rise to glomerulonephritis:

Answer 9

1) Deposition of circulating immune complexes in glomeruli
2) Antibodies to the glomerular basement membrane (GBM)
3) Local activation of the alternative complement pathway

Question 10

Immune-complex glomerulonephritis
- what is it?
- outcomes?

Answer 10

• deposition of immune-complexes in the glomeruli
• antigens in the antigen/antibody immune complexes can be non-glomerular and can be endogenous or exogenous
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• immune complexes can be deposited subendothelially, intramembranously, subepithelially and/or in the mesangium
• resulting disease is usually chronic and can be membranous and/or proliferative
  > membranous more common in animals
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• in short-lived cases, recovery is possible
• in chronic cases, the condition is progressive and the outcome worse

Question 11

Anti-glomerular basement membrane (Anti-GBM) glomerulonephritis
- what occurs?

Answer 11

• antibodies react to normal components of the basement membrane
  > rare in domestic animals

Question 12

common feature of all three mechanisms of glomerulonephritis?
- what happens due to this?

Answer 12

• Complement activation
• Local complement fixation leads to neutrophil chemotaxis
  > Neutrophils, while trying to phagocytose the immune complexes release lysozomal enzymes, arachidonic acid metabolites, and oxygen-derived free radicals which all damage the glomerular basement membrane
• Complement components also can initiate coagulation, thrombosis, and fibrinolysis

Question 13

gross appearance of glomerulonephritis

Answer 13

• acute glomerulonephritis may be unapparent, or the kidney may be mildly to markedly enlarged, pale, edematous, and soft, with glomeruli sometimes visible as small red dots; hemorrhages are sometimes present
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• chronic lesions > fibrosis > shrunken and contracted kidney with the capsule sometimes adhered and a granular appearance to the capsular surface
  > cortex uniformly thin, junction with medulla less apparent

Question 14

Glomerulonephritis is common in what species? type? how common?
- causes?

Answer 14

Dogs:
- usually membranoproliferative
- one of the leading causes of renal failure
- seen with pyometra, and many other infections such as Lyme disease
> also in familial glomerular diseases (Samoyeds, Bull terriers, English cocker spaniels, and Bernese mountain dogs)
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Cats:
- also common
- usually membranous, often resulting in renal failure and/or nephrotic syndrome
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Horses:
- also common
- usually proliferative
- rarely see renal failure

Question 15

Acute glomerular disease
- is it common?
- species and causes?

Answer 15

• unusual
• can occur in dogs: VTEC > renal glomerular thrombi, cutaneous thrombosis > infarcts
• pigs: PCV2

Question 16

amyloidosis - what is it? types?

Answer 16

amyloid is deposited extracellularly and in the walls of small blood vessels
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Four types of amyloid exist, occurring in five different types of amyloidosis:
1) Reactive (aka secondary or AA) amyloidosis
2) Immunoglobulin derived (aka primary or AL) amyloidosis
3) Familial amyloidosis
4) Apolipoprotein AI amyloidosis (apoAI)
5) Islet amyloid polypeptide amyloidosis

Question 17

Reactive (aka secondary or AA) amyloidosis
- how common?
- when does it occur?
- protein involved?

Answer 17

• most common in domestic species
• seen in persistent inflammation / infection or neoplasia
• derived from serum amyloid A – an acute phase protein

Question 18

Immunoglobulin derived (aka primary or AL) amyloidosis
- how common?
- origins?

Answer 18

• uncommonly seen in dogs, cats, and horses
• Derived from light chain immunoglobulin
• it is seen in abnormal conditions of plasma cells

Question 19

Familial amyloidosis - what is it?

Answer 19

• can be AA or AL
• Genetic basis not always known
• AA form seen in beagles, Shar Peis, grey collies, English foxhounds and Abyssinian, Siamese, and Oriental cats
• The AL form had been reported in a Holstein with bovine LAD

Question 20

Apolipoprotein AI amyloidosis (apoAI) - when is this seen? where?

Answer 20

found in older dogs in the pulmonary vasculature

Question 21

Islet amyloid polypeptide amyloidosis - when / where is this seen?

Answer 21

• seen in the pancreatic islets of cats with non-insulin dependent diabetes mellitus

Question 22

renal deposition of amyloid
- species differences
- who is most commonly affected?

Answer 22

deposition usually species specific
- Cats and cattle usually develop medullary amyloid
- other species > glomerular amyloid
- Older dogs are most commonly affected by amyloidosis with the cause rarely apparent

Question 23

Glomerular amyloidosis usually results in what? common complication? why?

Answer 23

• massive proteinuria without renal fibrosis
• Nephrotic syndrome and thrombosis of the renal vein is a more common complication in this disease
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• Nephrotic syndrome is a clinical condition and occurs when there is hypoproteinemia/hypoalbuminemia, hyperlipidemia with elevated cholesterols, triglycerides and other lipids, and edema
• Thrombosis occurs because of a loss of antithrombin III and tissue plasminogen activator

Question 24

Nephrotic syndrome - what is this?

Answer 24

• clinical condition
• hypoproteinemia/hypoalbuminemia, hyperlipidemia with elevated cholesterols, triglycerides and other lipids, and edema

Question 25

clinical relevance of amyloid deposition in renal medulla

Answer 25

Deposition of amyloid in the medulla is less-often clinically relevant though it can cause papillary necrosis

Question 26

classic appearance of renal amyloidosis

Answer 26

- pale, enlarged, firm - On removing the capsule, the surface is stippled yellow (glomeruli) and grey (dilated tubules) - cortex enlarged and stippled

Question 27

Chemical induced glomerular disease - how does it occur?

Answer 27

Chemicals can: - directly injure the glomerulus (epithelium and/or endothelium) - alter blood flow to and/or through the kidney - stimulate immune-complex disease