8.1-2 Glomerular pathology Flashcards
What’s the triad of clinical signs for Nephritic Syndrome?
(Blocked filter) Haematuria Hypertension Reduced GFR
Why do erythrocyte casts often appear the urine of someone with nephritic syndrome?
Nephritic syndrome occurs following inflammation of the glomeruli. Inflammation damages the endothelium, causing blood (and RBC’s) to leak into the nephron. The erythrocytes aggregate in the nephron tubule and take its shape, causing the cylinder shaped casts in the urine.
What is urinary lithiasis?
Calculi (stones) in the urinary system
Why does Nephrotic syndrome cause hyperlipidaemia along with its characteristic triad of clinical signs?
The liver synthesises more albumin to replace urinary losses due to proteinurea. As it does this, it simultaneously synthesises lipids.
Why do the kidneys get bigger in early diabetic nephropathy?
(Hyperfiltration causes hypertrophy) Poorly controlled diabetes causes hyperglycaemia so more glucose is filtered into the nephron. (Filtered load = GFR x Plasma concentration). SGLT2 in the PCT facilitates reabsorption of glucose (into blood) using the Na+ gradient (1:1 ratio). More glucose and Na+ are reabsorbed (because SGLT2 is low affinity but high capacity) so the concentration of NaCl arriving at the Macula densa cells is reduced. They sense low [NaCl] and increase GFR leading to hyperfiltration. Hyperfiltration causes renal hypertrophy.
Describe the affinity and capacity of SGLT2 in the proximal convoluted tubule?
Low affinity, high capacity which makes it the main transporter in glucose reabsorption.
How do Macula densa cells increase GFR? CHECK
Tubulo-glomerular feedback: Macula densa cells of the distal convoluted tubule sense the concentration of NaCl in the nephron. If it’s low, they secrete prostaglandins to act on Juxtaglomerular cells and stimulate renin release. Renin initiates RAAS pathway to raise blood pressure, thus RBF and GFR via Ang 2 mediated vasoconstriction and aldosterone mediated reabsorption of water via insertion of ENac channels in the CD. Prostaglandins also cause dilation of the glomerular afferent arteriole to increase RBF thus GFR.
How does activation of RAAS in nephrotic syndrome contribute to the oedema?
Proteinurea in nephrotic syndrome reduces the capillary oncotic pressure and water moves into the interstitial fluid via Osmosis (causing generalised oedema). Reduction in blood volume lowers the MAP which activates RAAS to raise bp via aldosterone mediated water resorption and Ang 2 vasoconstriction. However, the low oncotic pressure in the capillaries means the reabsorbed water leaks into the tissues, worsening the oedema.
When is Renin secreted by the Juxtaglomerular cells?
1) Low Bp. Juxtaglomerular cells surrounding the afferent arteriole detect low BP and secrete Renin in response.
2) Sympathetic stimulation of the JG cells. Nerve endings finish on the JG cells.
3) Low [NaCl] in the DCT sensed by the Macula Densa cells. The MD cells secrete prostaglandins that act on JG cells to stimulate Renin secretion.
Why is minimal change disease called this?
For years, histology showed either no change or a minimal cgnage in the appearance of the glomeruli (GBM intact). Later, electron microscopy allowe dthen to visualise characteristic loss of foot processes of podocytes.
What causes minimal change disease?
Who does it occur in?
Unknown circulating immune factor damaging podocytes. Considered to have some immune involvement because it responds to steroids (immunosuppressants).
Children aged 2-6 years
What is the pathophysiology of membranous glomerulonephritis?
Who does it occur in?
Antibodies bind PLAR-2 antigen on the podocytes leading to immune complexes deposited in the glomerular basement membrane. This activates complement which destroys podocytes and impairs the filtration specificity of the GBM causing nephrotic syndrome.
Most common cause of glomerularnephritis in adults
How does renal amyloidosis cause nephrotic syndrome?
Amyloidosis describes diseases where abnormal proteins (amyloid fibrils) are deposited in tissues. In the kidney, this damages the filtration barrier leading to nephrotic syndrome.
Describe the histological changes to the glomeruli during; i) early diabetic nephropathy ii) late diabetic nephropathy
Early; thick glomerular basement membrane which increases the pore size leading to microalbuminuria and mesangial expansion (which leads to a leaky GBM). (Also have large kidneys due to hyperfiltration and consequent renal hypertrophy). Late; Kimmelstiel- Wilson nodules, glomerulosclerosis and hyalinsation of arterioles (thickening of their walls).
What are Kimmelstiel-Wilson nodules?
Nodules of hyaline material deposited in the glomeruli due to increased synthesis of mesangial matrix (mesangial expansion occurs early in diabetic nephropathy).
What are the 3 filtration layers of the glomeruli?
(Superficial to deep)
Podocyte foot processes and filtration slits, glomerular basement membrane, fenestrated epithelium.
What is crescentric glomerular nephritis?
A histological appearance of the glomerulus indicating severe and rapid glomerular damage. The crescents are layers of epithelial/ fibrous proliferation occupying Bowman’s space and potentially compressing the capillary loops.
