Nephritic And Nephrotic Syndrome/ PBL B10 W1 Flashcards
1
Q
Normal kidney GFR
A
180L of plasma, where 1.5L leaves as urine
2
Q
How do kidneys affect prostaglandin synthesis?
A
When there is renal hypoperfusion (low kidney blood flow), increased prostaglandin synthesis to increase vasodilation of vessels.
3
Q
How does increased sympathetic tone of kidneys occur?
A
Activation of renal B1 receptors
4
Q
What is the HCO3-/CL- antiporter channels?
A
AE2 channels
5
Q
What is the HCO3-/Na+ symporter channels?
A
NBC1 channel
6
Q
Where does urea reabsorption occur?
A
Half is absorbed in the PCT and the rest is excreted out in the urine.
7
Q
When is Na+ secreted into the filtrated?
A
Never
8
Q
Where does majority of K+ reabsorption occur?
A
PCT
9
Q
Where does water reabsorption occur?
A
1) PCT
2) Loop of Henle
The rest is reabsorbed in the collecting duct
10
Q
Nephrogenic diabetes insipidus
A
Excessive urination mistaken for diabetes mellitus- occurs due to ADH deficiency because of lesion in posterior pituitary gland. Or, Mutation in aquaporin channels that leads to excess water loss in urine
11
Q
When are ANP levels elevated?
A
Released by atrial myocytes in response to atrial distention. Pathologically, increased levels related to heart failure.
12
Q
When are BNP levels elevated?
A
Released by heart ventricles and brain. Pathologically, increased levels are related to heart failure.
13
Q
How does ADH affect the kidney?
A
Insertion of aquaporin channels into collecting duct via V2 receptors and permeability of urea. Acts on V1 receptors to cause smooth muscle contraction of blood vessels.
14
Q
What are the types of primary nephrotic syndromes?
A
Minimal change disease
Focal seggmental glomerulitis
Membranous nephropathy/ Membranoproliferative glomerulonephritis
15
Q
Effect of ACE
A
Induces afferent arteriole constriction and causes elevation of bradykinin levels
16
Q
Indication of ACE inhibitor
A
Hypertension
Myocardial infarction
Congestive heart failure
Diabetic nephropathy
17
Q
Diabetic nephropathy
A
High levels of glucose of blood entering kidneys causes glycation of type 4 collagen in kidney basement membrane in efferent arteriole, causing damage so increased deposition of type 4 collagen occurs. This leads to vasoconstriction of efferent arteriole and increases the GFR, leading to hyperfiltration which results in renal vessel damage. To relieve this, ACE inhibitors induce vasodilation.
18
Q
Congestive heart failure
A
Failure of the heart in systole that cannot pump hard enough or diastole where the pre-load is low, so ventricles do not fill enough. This may cause blood to back up into the pulmonary arteries and cause dyspnoea, systemic congestion, and higher BP.
19
Q
Cause of L sided congestive heart failure
A
L sided is caused by ischaemia due to atherosclerosis, hypertension that causes cardiac hypertrophy and narrowing of the arterioles. In response to diastole HF, heart chamber may grow and cause muscles to weaken. L sided causes blood to flow backwards and affect the source in the lungs primarily
20
Q
Cause of R sided congestive heart failure
A
Right sided heart failure is generally a byproduct of left sided heart failure. It is also caused by chronic lung disease that causes the pulmonary arteries to constrict and create high BP. This leads to systemic congestion in the body, creating pitting oedema and enlarged JVP.
21
Q
Contraindication of ACE inhibitor
A
Foetal toxicity and co-administering with NSAIDS which will result in decreased GFR
22
Q
Types of acute kidney injury
A
Pre-renal
Intrarenal
Post renal
23
Q
Pre-renal AKI
A
Decreased blood flow entering kidneys.
Lower blood volume caused by hypovolemia (blood loss) and haemorrhage or fluid loss via vomiting or skin burns.
Issue with the heart like congestive heart failure means not enough blood is pumped to the kidney.
The vessel itself may be affected such as stenosis or embolism.
24
Q
What is pre-renal AKI linked to?
A
Generally linked to lower BP, so aldosterone is released to increase H20 and Na+ reabsorption in blood for increasing BP, but this also increases urea uptake, worsening azotaemia.
25
Intrarenal AKI
Issue within the glomerulus
such as:
Acute tubular necrosis
Glomerulonephritis
Vascular diseases
Acute interstitial nephritis
This affects the glomerular integrity and allows large proteins and fluids to leak, reducing GFR and causing oedema, oliguria
26
Acute tubular necrosis
Intrarenal AKI where epithelial cells of tubular cells of nephrons die due to ischaemia caused by pre-renal injury, affecting mainly the PCT and ascending limb. The dead cells build up and create high pressure area, disrupting filtration down pressure gradient, reducing GFR for removing toxic waste like urea and creatinine and generating urine causing oliguria.
27
Causes of acute tubular necrosis
Damage from external factors like contrast dyes for X-rays, aminoglycosides, heavy metal, myoglobin (from damaged muscles) and uric acid. Uric acid is a waste product of cancer cell death in treatment.
28
Acute interstitial necrosis
Type 1 or Type 4 hypersensitivity affecting connective tissue of interstitium. Caused by NSAIDS, diuretics or penicillin.
29
Post renal AKI
Caused by obstruction to the ureter. Congenital malformations and neurogenic bladder that leads to multiple sclerosis
30
Features of AKI
Urea retention as azotemia resulting in uremic frost, neurological symptoms and GI issues. Urea and creatinine levels in the blood are measured in a ratio called BUN. Most of creatinine is excreted in the body but urea levels undergo more regulation in increase and decrease, because it is reabsorbed passively via Na+ and H20 uptake. Urea levels in the blood are higher than creatinine.
31
What happens in post renal AKI?
Backflow of fluid and urine, increasing pressure and disrupts the pressure gradient. This reduces GFR and causes retention of urea in the blood because it can’t enter nephron.
32
Nephron categories
Short cortical nephrons: majority of all kidney nephrons located in cortex
Juxtamedullary nephrons: located mainly in medulla and have a greater effect at concentrating urine
33
Vasopressin/ADH
Produced from the posterior hypophysis and released into circulation in response to low Na+ and H20 levels and increases polypsia. It causes insertion of aquaporin channels in the DCT and collecting duct. Causes vasoconstriction and increase in peripheral resistance.
34
Aldosterone
Released via action of angiotensin 2 on adrenal medulla. It acts on the DCT and the principal cells of the collecting duct to increase expression of the Na+/K+ ATPase pump. Also increases expression of Na+ channels.
35
Nephrotic syndrome
Damage to the podocytes of the glomerulus which results in the loss of proteins into the urine which becomes frothy. Proteins leak into urine filtrate causing hypoalbumeniemia. This induces increased liver production of proteins which increases lipid levels as a byproduct, causing hypercholesterolemia. The loss of albumin disrupts oncotic pressure and leads to peripheral oedema.
Proteinuria, hypoalbuminuria, Hyperlipidaemia and oedema. Complications are thrombosis due to low albumin
36
Cause of nephrotic syndrome
Minimal change disease
Focal segmental glomerulosclerosis
Membranous nephropathy
Diabetes mellitus
Amyloidosis
37
Common cause of nephrotic syndrome in children
Minimal change disease: commonly occurs after viral infection, with cytokine mediated damage of podocyte foot processes, disrupting protein retention. There is sudden onset and sudden offset and this disease is responsive to steroids.
Minimal change disease has little change when seen under an electron microscope.
38
What are the features of minimal change disease on electron microscopy?
Extensive podocyte foot process effacement, however this is non-specific. Corticosteroids are the main staple of treatment.
39
Most common cause of primary nephrotic syndrome in adults
Focal segmental glomerulosclerosis which is assoicated with triggers like podocyte injury; scar tissue formation occurs on regions of the glomerulus and hyaline occlusion of capillary loops occur. Primary FSG is idiopathic and secondary FSG is related to Congenital defects or autoimmune conditions. It must be diagnosed by
40
What are the secondary causes of focal segmental glomerulosclerosis?
Viruses like HIV and parvovirus
Other glomerular diseases with increased risk of podocyte injury like minimal change disease
Sickle cell disease, obesity, renal agenesis
41
What are the features of focal segmental glomerulosclerosis on imaging?
FSG shares similarities with minimal change disease, however has a worse prognosis as adults have a poorer response to steroids. Light microscopy shows focal segmental sclerosis. Electron microscopy shows effaced podocyte food process
42
What is the treatment of focal segmental glomerulosclerosis?
Immunosuppressive medication such as corticosteroids like prednisone in combination with cyclosporine and maintaining blood pressure control with ACE inhibitors and ARB
43
Membranous nephropathy
Autoimmune condition where there is subepithelial immune complex deposition between podocytes and basement membrane, involving IgG and C3 convertase activity that causes podocyte injury Via MAC complex formation. This can result in proteinuria, nephrotic syndrome and a high risk of renal vein thrombosis due to the loss of anti-thrombin which would be bound to heparin.
44
What is the cause of primary membranous nephropathy?
The target is the phospholipase A2 receptor expressed on the podocytes of the kidney.
45
What are the causes of secondary membranous nephropathy?
Secondary causes are generally related to autoimmunity, drugs and infection
Graft versus host disease
Haematopoietic stem cell transplantation
Sarcoidosis
Autoimmune disease
46
What are the diagnostic features of membranous nephropathy?
Diffuse thickening of the glomerulus basement membrane on al glomeruli and presence of IgG and C3 complement protein in the sub epithelium with effacement of Podocyte and expansion of glomerular basement membrane.
47
What is a risk of membranous nephropathy?
Renal vein thrombosis- this occurs due to hypoalbuminemia because albumin binds to heparin. There is also loss of anti-thrombin.
48
Why is albumin important in clotting?
Albumin is a carrier for anti-thrombin and heparin cofactor which regulate clotting. This leads to excess clotting in blood and thrombosis.
49
Membranoproliferative glomerulitis
Membranous glomerulopathy diagnosed on biopsy with mesangial expansion and hypercellularity which causes splitting of the GBM and thickening of capillary wall. It can manifest as nephrotic or nephritic syndrome.
Immune complexes can deposit and induce inflammatory cytokine damage that promotes platelet recruitment and complement activation
It is typically caused by lupus or chronic inflammation.
50
What is the presentation of glomerulonephritis?
Presentation with features of nephritic and nephrotic syndrome and can have fatigue, anorexia and weight loss with anaemia.There is persistent proteinuria and decline of renal function
51
What is type 1 membranoproliferative glomerularitis?
Immune complex deposition occurs in the subendothelium, between the podocytes and glomerular basement membrane, causing splitting of GBM and mesangial in growth. It is associated with hepatitis B and C and is a Nephrotic and nephritic condition.
52
What is type 2 membranous membranoproliferative glomerulitis?
AKA dense deposit disease where IC deposition occurs in the glomerular basement membrane, causing splitting of GBM and there is over activation of the complement cascade due to C3 nephritic factor which stabilises and causes overactivation of alternative complement pathway. Can manifest as a Nephrotic and nephritic condition.
53
What are the secondary causes of membrane proliferative glomerulonephritis?
autoimmune diseases such as lupus, sjogren syndrome and arthritis
Neoplasias like leukaemia and lymphoma
Infection like hepatitis B and C
54
What is the secondary cause of nephrotic nephropathy?
Diabetic nephropathy
Sytemic lupus
Amyloid nephropathy
54
What is the presentation of IgA nephropathy?
fever, hypertension, oedema, haematuria and proteinuria. There is alveolar bleeding that can manifest as haemoptysis and haematuria.
54
What is the pathology of IgA nephropathy?
Typically Triggered following an infection of the URT or gastroenteritis where there is deficiency in galactlysation of IgA which leads to formation of antibody-antigen complexes in the mesangium, causiing excess activation of alternate complement pathway.
55
Most common primary nephropathy in elderly patients
Amyloid nephropathy: deposition of abnormal misfolded proteins called amyloid in the kidney interstitium arteries, arterioles and mesangium that replace the extracellular matrix and causes pressure atrophy of kidneys and leads to nephrotic syndrome. It typically occurs due to light chains or serum amyloid precursor proteins
Amyloid nephropathy has a poor prognosis of only a few months.
55
What are the features of IgA nephropathy on biopsy?
presence of mesangial IgA deposition causing mesangium expansion and hypercellularity with microscopic haematuria and focal proliferative glomerulopathy There is the presence of anti-glycated antibodies
56
How is IgA nephropathy treated?
ACE inhibitors and ARBs to reduce glomerular pressure
Corticosteroids to reduce inflammation
56
What are the features of amyloid protein on biopsy?
Presence of beta-pleated sheet structure and accumulation of eosinophilic material in mesangium and capillary loops, stainin positively red with Congo red and apple green bifringence due to beta pleated sheets.
57
Primary amyloid nephropathy
Inability to degrade antibody immunoglobulin light chain associated with Multiple myeloma which is cancer of the bone marrow.
58
Secondary amyloid nephropathy
Caused by chronic inflammatory conditions due to cytokines increases production of excess serum amyloid precursor proteins serum amyloid a (SAA) which acts as an acute phase reactant. This occurs with coniditions such as rheumatoid arthritis, familial Mediterranean fever, IBD and infections
59
How is amyloidosis diagnosed?
Serum and urine electrophoresis with light microscopy, Congo red stain, haemotoxylin stain for eosinophil and apple green bifringence.
60
What is the treatment of amyloid nephropathy?
Haematopoeitic stem cell transplant and steroid therapy to reduce inflammation.
61
Presentation of glomerulonephritis
Loss of proteins in urine such as antithrombin, protein C and S which increases hypercoagubility so increased thrombosis and embolus
Hypertension
Loss of immunogoblins
Hypercholesterolemia
Sytemic oedema
62
What is nephritic syndrome?
Inflammation of the glomerulus which becomes hypercellular, characterised by, haematuria, mild proteinuria and hypertension, azotemia and oliguria
63
Nephritic syndrome
Post streptococcal glomerunephritis
IgA nephropathy
Small vessel vasculitis
Goodpasture syndrome
Alport syndrome
Membranoproliferative glomerulonephritis
64
What is rapidly progressing glomerulonephritis?
Nephritic syndrome initiated by capillary injury that causes hyper proliferation of parietal epithelium, creating extra-capillary aggregates which form in the Bowman's space and compress the capillary tuft (glomerulus). This can induce immune complex deposition and is assoicated with nephritic syndromes.
65
What causes crescent linear immune complex deposition?
Goodpasture’s syndrome
66
What causes crescent granular subendothelial immune complex deposition?
Diffuse Proliferative glomerulonephritis
67
What causes crescent granular subepithelial immune complex deposition?
Post-streptococcal glomerulonephritis
68
Post-streptococcal glomerulonephritis
Mos common post-infectious glomerulonephritis:
Occurs weeks after infection with Group A beta-haemolytic strep like streptococcus pyogenes which causes the generation of anti-streptolysin antibodies (ASO) that results in subepithelial immune complex deposition in the glomerulus and mesangial proliferation, leading to excessive activation of alternative complement pathway causing nephritic syndrome.
69
What are the diagnostic features for post-streptococcal glomerulonephritis?
Anti-DNAse B, hyaluronidase and ASO-
may not be present if antibiotic therapy has started
Diffuse neutrophil proliferation that is “exudative” due to abundant polymorphonuclear cells with subepithelial immune complex deposition. **Starry sky appearance of C3** scattered throughout mesangium and capillary walls.
70
How do patients present with post-streptococcal glomerulonephritis?
Oedema, haematuria and proteinuria
71
What can cause a false negative ASO antibody?
Ongoing skin infection due to skin destruction releasing cholesterol that irreversibly binds to streptolysin O.
72
How is post-streptococcal glomerulonephritis treated?
typically self-limiting however can be treated with course of antibiotics and supportive care to manage hypertension.
73
Nephritic syndrome-presentation
Oliguria with haematuria,
Lesser Proteinuria associated with oedema
High BUN and creatinine
Kidney function deteriorates causing hypertension: due to Na+ and H20 retention
azotemia
oliguria
74
What is IgA nephropathy?
Deposits of IgA in the kidney which can occur **a few days post-infection** and result in alveoli bleeding and glomeruli bleeding. It is a nephritic syndrome and the most common chronic glomerulonephritis in children
79
What is IgA nephropathy associated with?
Henoch Schonlein purpura, a non-blanching but palpable purpuric rash on the lower limbs due to IgA deposits in the small blood vessels which induces fibrosis.
80
What are the features of Henoch Schonlein purpura?
It is characterised by puroura, joint pain, abdominal pain and kidney impairment.
Haemorrhage of the blood vessels can cause joint pain and reduce range of movement when affecting the knees. Abdominal pain is assoicated with gastrointestinal haemorrhage and cause bowel infarction.
81
When does H+ secretion stop?
Urine pH falls below 4.5
82
Where is the majority of buffering capacity in the body?
1) Cells perform 52%
2) EC space 43%
3) RBC
83
What are the features of chronic kidney disease?
Hypertension, peripheral oedema, uraemia and loss of mineral bone density.
84
What are the features of uraemia?
Fatigue, loss of appetite, anaemia, GI symptoms, increased infection risk and encephelopathy.
85
Polycystic kidney disease
Genetic disease charactersied by the formation of cysts in the tubular epithelia which causes dysfunction and reduces GFR.
86
How does polycystic kidney disease present?
Begins as asymptomatic but may progress and cause
Hypertension
Hameaturia
Fullness in abdomen
Polyuria
87
Anti-glomerular basement membrane disease
Type 2 hypersensitivity that is IgG mediated against Type 4 in the glomerular basement membrane which causes bleeding. It is a nephritic syndrome and also presents with haemoptysis because it targets the type 2 collagen in alveoli.
88
What is the clinical presentation of anti-glomerular basement membrane disease?
Autoimmunity affects the collagen in both the kidneys and the lungs, causing an acute onset of haemoptysis with oedema, haematuria and typical features of nephritic syndrome such as hypertension. Most commonly affects men in their 20s and 30s with a second peak in their 60s.
Anti-glomerular basement membane disease is associated with HLA-DR2 and environmental factors such as tobacco smoke and hydrocarbons
89
How is anti-glomerular basement membrane disease diagnosed?
ELISA antibody test for anti-glomerular basement membrane antibodies
Proliferative glomerulonephritis with LINEAR deposits of immunoglobulin, and areas of necrosis and crescents
90
What is the treatment of anti-GBM disease?
Plasma Exchange to remove circulating anti-GBM antibodies and immunosuppressants to orevent antibody formation
91
What is diffuse proliferative glomerulonephritis?
Subendothelial immune complex deposition which results in thickening of capillary wall and presents with symptoms of nephrotic AND nephritic syndrome.
92
What is Alport syndrome?
Nephritic syndrome which is a genetic condition caused by mutation of type 4 collagen in the glomerular basement membrane, creating large pores for the passage of substances that causes loss of blood and protein into the urine that leads to sclerosis of basement membrane and renal failure.
Kidney failure develops over many years and there is childhood onset of hearing loss, myopia and sensineural deafness.
93
What are the features of Alport syndrome?
Most comm subtype is an X linked recessive condition due to a mutation of COLA45. Less common are mutations of COLA3 and COLA4 but all 3 subtypes form part of the basement membrane in post-infancy.
94
What are the diagnostic features of Alport syndrome?
->microscopic/gross haematuria with proteinuria
->Vision/hearing deficiency
Skin/renal biopsy shows absence of any degraded collagen
->Microscopy shows glomerulosclerosis and interstitial fibrosis , with irregular thinning and thickening of the glomerular basement membrane and splitting in a “Woven basket appearances
95
What is the treatment of Alport syndrome?
management of proteinuria with RAAS inhibitors like ACE inhibitors and ARBs
Supportive treatment with fluids.
96
What is the lining of the kidney?
Epithelium of fenestrated endothelium
Connective tissue of the glomerular basement membrane which is negatively charged to repel proteins
Podocytes which have foot processes
97
Which nephrotic diseases have a higher risk for thrombosis?
Membranous nephropathy
Lupus arthritis
98
What is lupus nephropathy?
Autoimmune disease driven by anti-ds DNA antibodies that form overtime due to epitope spreading which cross react with renal structures and cause immune complexes to form and deposit into the mesangium, sub epithelium and endothelium, stimulating a Type 3 hypersensitivity reaction. It can present as either nephrotic or nephritic syndrome.
99
What is the presentation of lupus nephritis?
Clinical presentation varies and includes proteinuria, haematuria, hypertension, oedema and raised serum creatinine. It can result in pulmonary renal syndrome where alveolar bleeding and glomerulonephritis due to vessel damage.
100
What are the diagnostic features of lupus nephropathy ?
Crescent shaped swelling at the site of deposition
Wire loop pattern of glomerulus due to thickening
Treatment is immunosuppression with corticosteroids and cyclophosphamide, or in extreme causes immune therapiesa.
101
How does small vasculitis occur in the kidneys?
Anti neutrophil cytoplasmic antibodies (ANCA) vasculitis is mediated by IgG against neutrophil granules such as proteinase 3 and involves the arterioles of the kidneys and glomerular capillaries where conditions like lupus and IgA nephropathy predispose to vessel damage,
102
What are the categories of ANCA vasculitis?
Microscopic polyangitis
Wegener’s disease
Churg-Strauss syndrome
103
What are the features of Wegner’s disease?
It is the most common cause of proteinase 3-mediated ANCA damage, generating oxygen free radicals affects vasculitis.
Causes granuloma in respiratory tract and kidneys with necrotising glomerulonephritis due to ischaemia, causing an increase in BP.
Involves the kidneys, nasopharyngeal skin, lungs and GIT. (haemoptysis)
104
What are the features of microscopic polyangitis?
Peri-nuclear ANCA directed towards myeloperoxidase on neutrophils. It affects the lungs and kidneys and causes necrotising glomerulonephritis and pulmonary capillarities.
105
What are the features of Churg-Strauss syndrome?
Caused by peri-nuclear antibodies which produces an eosinophil rich reaction that causes necrotising glomerulonephritis and causes granuomatous inflammation of the respiratory tract.
There is an association with allergic conditions such as asthma.
106
How is proteinuria managed?
Obtain 24 hour urine collection
Dietary protein restriction to red r intraglomeular filtration pressure
ACE inhibitors and ARBs to reduce intraglomeerular pressure
107
How is Hyperlipidaemia managed?
Dietary restriction with low fat and cholesterol
Statin and lipid lowering drugs
