Week 4 - I(2) - Glomerulonephritis lecture - treatment part Flashcards
What is the first and second most common causes of end stage renal failure?
Dibetes - 1st Chronic glomerulonephritis - 2nd
Acute GN is an important treatable cause of Acute Renal Failure What is glomerulonephritis?
Immune mediated disease of the kidneys affecting the glomeruli
What happens secondary to the glomeruli being damaged by glomerulonephritis?
secondary tubulointerstitial damage
What is the yellow shown in the picture?
These are the podocytes - specialized cell of the bowmans capsule that wrap around the capillaries
What are the three layers of the glomerular membrane?
Fenestrated capillaries Basemant membrane (lamina propria) Podocytes with filtration slits
The glomerular membrane is a size and charge selective barrier What does glomerulonephritis do to the barrier?
It causes damage to the barrier allowing blood and protein to leak through - haematuria and proteinuria
There is proliferative and nonproliferative lesions occuring during gloerulonephrtiis What does damage to the podocytes lead to?
Damage to the podocytes leads to a non-proliferative lesion and protein in the urine
Damage to what leads to a proliferative response from the kidneys? What is in the urine?
Damage to the endothelium or mesagnial cells leads to a proliferative response and red blood cells in the urine
What is the function of the mesangial cells?
They are supporting cells between capillaries holding the matrix together Secrete phagocytes if there is antigen
Why is it that protein will appear in the urine if there is damage to the podocytes?
This is because the negative charge of the podocytes ill be lost and the large proteins will not be repelled The size/charge specific barrier is lost
Damage to the mesangium and endothelial results int he release of what?
Results in proliferation, and attracts inflammatory cells
24 year old man incidentally found to have ++ blood and + protein on dip, BP 148/92. Protein quantified at 0.7g/day. Creat 72. What glomerular cells are most likely to be injured? (endothelial, mesangial or podocytes)
The cell mot likely to be injured is the mesangial cells If damage endothelial cells – the creatinine would not be normal as the filtration rate would be damaged
When carrying out urinalysis, what is suggestive of glomerular disease? One thing in particular
Proteinuria
How is the amount of protein quantified?
24hour urine preotein or protein:creatinine ratio
What aounts of proetin suggest nephrotic syndrome? What is done after quantifying the protein to find out the cause?
24 hour urine protein - 3g/day Protein:creatinine ratio - 300mg/mmol
Nephrotic syndrome will also present with hypoalbuminaemia, what level of albumin is this?
Less than 25g/l
When looking at urine microscopy of the red blood cells, how can this help to identify where the urine came from?
Urine microscopy of red blood cells are dysmorphic is the bleed is coming from the glomerulus - have to be squashed through isomorphic if lower urinary tract
A patient’s urinary casts can also be looked at on microscopy What does a red cell cast inidcate?
This indictes nephritic syndrome - glomerulonephritis
What does granular casts indicate?
Inidcates chronic kidney disease or acute tubular necrosis (muddy brown casts)
Which type of casts indicate nephrotic syndrome?
Fatty catsts in the urine
What are the features of nephritic syndrome?
Acute renal failure Oliguria Haematuria High blood pressure RBCs and granular casts Oedema/fluid retention Azotemia
What type of process is nephritic syndrome indicative of? What is azostemia?
It is highly suggestive of a non-proliferative process affecting the endothelial/mesangial cells Azostemia is abnormally elevated levels of nitrogen in the blood using due to renal dysfunction preventing filtration
What is oliguria defined as?
it is a urinary output of less than 400ml/day
What is the typical triad of nephritic syndrome features then?
Hameaturia Oliguria Hypertension (azotemia)
What type of process affecting what is seen in nephrotic syndrome ?
This would be a non-proliferative proces causing podocyte disruption
What are the clinical features of nephrotic syndrome?
Proteinuria - greater than 3g/day Hypoalbuminaemia - less than 25g/l Oedema Hyperlipidaemia Usually renal function is normal
Does kidney function usually decline in nephrotic or nephritic syndrome?
Kidney function usually declines in nephritic syndrome
What are complications of nephrotic syndrome?
Renal vein thrombosis Infections Volume depletion - if overuse of diuretics
How does GN differ from a non glomerular disease like Interstitial Nephritis?
intersitial nephritis is a disease affecting the interstitium
What is the main cause of glomerulonephritis?
Idiopathic
What is next most common cause of glomerulonephritis after idopathic?
This would be due to post streptococcal inflammation - streptoccoal antigen will circulate and deposit in the glomerulus
What are the investigations carried out to check for glomerulonephritis?
Renal biopsy and then - A renal biopsy is carried out and then a light microscopy – then immunofloursecne (stained the kindey for IgG), and then electon microspy – good to see the glomerular membrane
HISTOLOGICAL CLASSIFICATION in GN What does proliferative or non proliferative usually refer to?
usually refers to the presence or absence of mesangial cell proliferation
What does focal or diffuse glomerulonephritis refer to?
Less than or greater than 50% of the glomeruli are affected
Global/Segmental (all or part glomerulus affected) What does crescent shapes on histology mean?
Rapid progressive glomerulonephritis - epithelial cell extracapillary proliferation
What is the aims of treatment for glomerulonephritis?
Decrease proteinuria Induce remission of nephrotic syndrome Preserve long term renal function
Treatment of glomerulonephritis is NON-IMMUNOSUPPRESSIVE and IMMUNOSUPPRESSIVE What are non-immunosupressive treatments aimed at?
Aimed at lowering the blood pressure of the patient
What is the target blood pressure in GN? What is given?
Target blood pressure is 130/80 Give ACEi/ARBS to try maintain this blood pressure
What can be given for the oedema and the hyperlipidaemia in glomerlonephrtiis?
Hyperlipidaemia - statin Oedema - diuretic for symptoms - increases fluid excretion
Omega 3 fatty acids/ Fish oil What should you watch the intake of in GN?
Watch the intake of salt
Non immunosuppressive treatment is usally given for nephrotic syndrome as it is non proliferative and does not require it What is the treatment given for nephritic syndrome?
This owould be immunosuppressants - corticosteroids and cyclophosphamide
What is the main dietary and pharmacological treatment of glomerulonephritis then?
Dietary - fluid restrict and salt restrict ACEI/ARBS Diuretics for oedema Anticoagulants? IV alumin if completely depleted
the aim of treatment is to control proteinuria and induce sustained remission What is remission in nephrotic syndrome?
Complete remission - proteinuria <300mg/day Partial remission <3g/day
What are the risks of immunosuppressing a patient who is nephrotic?
Infection is the main risk
