urinary system notes pt 5 Flashcards
glomerulus primary function, structure
- how much filtration do they do per day?
- 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
glomerulus - what substances are filtered out of the plasma in the glomerulus? what is retained?
- 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
Terms used to specify the distribution/severity of glomerular disease:
- diffuse
- focal
- global
- segmental
- mesangial
- 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
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:
- 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
what are mesangial cells?
- 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
Failure of function of the glomerulus occurs when:
- there is damage to the endothelium, basement membrane, or glomerular epithelium
glomerular disease usually results in what sort of lesions? what is the outcome from a functional standpoint?
- 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
<><> - Regardless of the initiating injury, the glomerular filter is affected and larger molecules (particularly protein) pass through
<><><><> - 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
what proceeds clinical signs of glomerular disease, and is often a major part of the clinical picture?
proteinuria
Generalized glomerulonephritis
- There are three main pathogenetic mechanisms that give rise to glomerulonephritis:
1) Deposition of circulating immune complexes in glomeruli
2) Antibodies to the glomerular basement membrane (GBM)
3) Local activation of the alternative complement pathway
Immune-complex glomerulonephritis
- what is it?
- outcomes?
- deposition of immune-complexes in the glomeruli
- antigens in the antigen/antibody immune complexes can be non-glomerular and can be endogenous or exogenous
<><><><> - 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
<><><><> - in short-lived cases, recovery is possible
- in chronic cases, the condition is progressive and the outcome worse
Anti-glomerular basement membrane (Anti-GBM) glomerulonephritis
- what occurs?
- antibodies react to normal components of the basement membrane
> rare in domestic animals
common feature of all three mechanisms of glomerulonephritis?
- what happens due to this?
- 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
gross appearance of glomerulonephritis
- 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
<><><><> - 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
Glomerulonephritis is common in what species? type? how common?
- causes?
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)
<><><><>
Cats:
- also common
- usually membranous, often resulting in renal failure and/or nephrotic syndrome
<><><><>
Horses:
- also common
- usually proliferative
- rarely see renal failure
Acute glomerular disease
- is it common?
- species and causes?
- unusual
- can occur in dogs: VTEC > renal glomerular thrombi, cutaneous thrombosis > infarcts
- pigs: PCV2
