Renal disease Flashcards
What are the major functions of the kidney?
- Excretion of metabolic waste products and foreign chemicals - including drugs
- Regulation of fluid, elecrolytes and acid/base balance
- Regulation of blood pressure - renin
- Regulation of calcium and bone metabolism
- Regulation of haematocrit - erythropoeitin
Desrcibe the anatomy of the kidneys:
- Location
- Landmarks
- Length
- Weight
- Amount of cardiac output
- Basic unit and what makes it up
- Retroperitoneal
- T12 to L3 on left and right is slightly lower
- Mean length is 11cm
- Male weight = 125-170g, female weight = 115-155g
- Recieve 20% of cardiac output
- Nephron - made up of a glomerlus, afferent and efferent arterioles and tubules
Describe the order at which filtrate passes through the nephron
- Blood is filtered at the glomerlus
- The filtrate is modified in the tubules - proximal convoluted tubule, loop of henle, distal convoluted tubule, collecting tubule and finally the collecting duct
What is the function of the proximal convoluted tubule?
- PCT actively resorbs sodium
- Hydrogen exchange to allow carbonate resorption
- Co-transport of amino acids, phosphate, glucose
- Potassium is also reabsorbed
Describe the function of the Loop of Henle
- Descening/ thin ascending limb is permeable to water but not ions or urea
- Ascending limb actively resorbs sodium and chloride
- Coutercurrent multiplier, aligned wit vasa recta
What is the function of the distal convoluted tubule?
- Impermeable to water
- Regulates pH via active transport (H/bicarbonate)
- Regulated sodium, potassium via active transport - aldosterone
- Regulates calcium - through PTH and 1,5-dihydroxycholecalciferol
What is the function of the collecting ducts?
- Resorbs water - principal cells and antidiuretic hormone
- Regulates pH - intercalated cells and proton excretion
- What are immune complexes?
- Whta happens to immune complexes in the kidney?
- An immune complex is a latticework of antibody and antigen - may be endogenous or exogenous antigens
- May deposit in the glomerlus causing an inflammatory response, complement activation and stimulation of inflammatory cells
May deposit at different rates and at different sites
What are the different signs and symptoms that occur in renal disease?
- Haematuria
- Proteinuria
- Uraemia
- Hypertension
- Oliguria/Anuria
- Polyuria
- Oedema
- Colic
What are the genitourinary malformations and issues that can occur in the kidney?
- Agenesis
- Renal fusion e.g. horse-shoe
- Ectopic kidney
- Renal dysplasia
- Pelvi-ureteric Junction obstruction
- Ureteral duplication
- Vesicoureteral reflux
- Posterior urethral valves
Describe adult polycystic kidney disease
- Inheritance
- Signs and symptoms
- Genes involved
- Complications
- Mono Dominant inheritance - 1:500
- Presents in adulthood with hypertension, flank pain and haematuria
- PKD1, PKDS2
- 10% risk of end-stage renal failure, PKD patients have a higher risk of developing Berry aneurysms and a higher chance of bursting
- When do cysts commonly develop?
- What is there an increased risk of when cysts develop?
- Cysts commonly develop in patients with end stage renal disease who are on dialysis - often they are multiple, bilateral and can be cortical or medullary
- There is an increased risk of development of malignancy - 7% at 10 years - most commonly papillary renal cell carcinoma
What are the main renal disease syndromes?
- Acute renal failure (Acute kidney injury)
- Nephrotic syndrome
- Isolated Urinary abnormalities
- Chronic kidney disease
- What is acute renal failure?
- What are the causes of the different types of acute renal failure?
- Pre-renal
- Renal
- Post renal
- Acute renal failure is a rapid deterioation in renal function (hours-days)
2.
- Pre-renal causes - failure of perfusion of the kidney
- Renal - acute tubular injury, acute glomerulonephritis, thrombotic microangiopathy
- Post-renal - obstruction
- What is acute tubular injury?
- What can predispose to it?
- Acute tubular injury is the commonest cause of acute renal failure. Tubular epithelial cells can be damaged by ischaemia, toxins e.g. contrast, Hb, myglobin and drugs
- Critical illness it is a common occurrence. Drugs that inhibit vasodilatory prostaglandins predispose e.g. NSAIDs
- Describe the pathophysiology of acute tubular injury
- Ischaemia/toxins/drugs affecting the tubules causes loss of polarity and brush border which is normal. Apoptosis of cells occur, and sloughing of viable and dead cells leading to luminal obstruction. Necrosis occurs and then viable cells spread and dedifferentiate to replace damaged cells
Failure of glomerulation filtration:
- Blockage of tubules by casts
- Leakage of tubules to intestinal space
- Secondary haemodynamic changes
- What is acute tubulo-intestinal nephritis?
- What causes it?
- What is the pathogenesis?
- Acute tubulo-interstitial nephritis is immune injury to tubules and intersitium
- Can be caused by:
- Infection
- Drugs - NSAIDs, antibiotics, Diuretics, Allopurinol and PPIs
3. Heavy interstitial inflammatory infiltrate with tubular injury, eosinophil infiltration and granuloma formation
- What is acute Glomerulonephritis?
- What does it present with?
- What are crescents?
- Acute glomerulonephritis is acute inflammation of glomeruli
- Presents with oliguria with urine casts containing erythrocytes and leucocytes
- Cresecents are proliferation of cells within the Bowman’s space - sign of acute renal failure
- What is Acute Cresentic glomerulonephritis?
- What is associated with it?
- What can it lead to?
- Acute cresenteric glomerulonephritis is caused by immune complexes. (Seen in anti-glomerular basement membrane diesease. Presence of Pauci-immune or anti-neutrophil cytoplasm antibodies)
- Aetiologies include SLE, IgA nephropathy and post-infectious glomerulonephritis
- Leads rapidly to irreversible renal failure
- What is is Anti-glomerular basement membrane disease and what is the pathogenesis?
- Ant-GBM is a rare and severe disease caused by antibodies directed against the glomerular basement membrane. Affects the C-terminal domain of Type 4 collagen, may cross-react with alveolar basement membrane leading to pulmonary haemorrhage
Linear deposition of IgG demonstratable on glomerular basement membrane
- What is Pauci-immune cresenteric glomerulonephritis?
- What antibodies is it associated with it?
- Pauci-immune cresenteric glomerulonephritis is caused by scanty glomerular immunoglobulin deposits
- Usually ANCA associated which triggers neutrophil activation and glomerular necrosis. Can lead to vasculitis elsewhere
- What is thrombotic microangiopathy and pathophysiology?
- What are the two types and what causes the two different types?
- Damage to the endothelium in glomeruli, arterioles, arteries leading to thrombosis. Red cells can be damaged by fibrin which can lead to microangiopathic haemolytic anemia and HUS
- Types: diarrhoea associated and non-diarrhoea associated
Diarrhoea associated:
- Bacterial gut infection such as with E.coli (hence link with HUS)
- Toxins released that target renal endothelium
Non-diarrhoea associated:
- Defects in regulation of complement
- Deficiency in ADAMTS13
- Drugs e.g. calcineurin inhibitors
- Radiation
- Hypertension
- Scleroderma
- Antiphospholipid syndrome (+/- SLE)
- What is nephrotic syndrome?
- What are the common signs?
- What conditions are associated with nephrotic syndrome?
- Nephrotic syndrome is a breakdown in selectivity of glomerular filtration leading to protein leak
- Common signs:
Proteinuria (>3.5g/day)
Hypoalbuminemia
Oedema
Hyperlipidemia
- Associated with:
- Primary glomerular disease, non-immune complex related e.g. minimal change disease
- Primary renal disease, immun complex mediated - membranous glomerulonephritis
- Systemic diseases - diabetes mellitus, amyloidosis and SLE
Describe minimal change disease
Minimal change disease is a glomerular disease that leads to large loss of protein in the urine. Is the most common cause of nephrotic syndrome in children
Generally responds to immunosuppression
Describe focal segmental glomerulosclerosis
Type of primary glomerular disease leading some glomeruli to become scarred. This can lead to renal failure and protein leakage. Non-immune complex related
Cause of nephrotic syndrome in children and adolescents
Describe membranous glomerulonephritis including pathogenesis
What antibody is associated with the disease?
Membranous glomerulonephritis is a form of primary renal disease and is immune complex mediated.
Associated with immune deposits on outside of glomerular basement membrane (supepithelial)
Primary disease is autoimmune - in 75% cases the antibody associated is against phospholipase A2 type M receptor (PLA2R)
Common cause of nephrotic syndrome in adults
- Describe diabetic nephropathy pathogenesis
- Describe the stages of nodular glomerulosclerosis in diabetic nephropathy
- Diabetic nephropathy affects 30-40% of people with diabetes. High glucose levels are directly injurious. Typically starts as microalbuminuria before progression to proteinuria and nephrotic syndrome
- Nodular Glomerulosclerosis
Stage 1- thickening of basement membrane on EM
Stage 2 - Increase in mesangial matrix, without nodules
Stage 3- Nodular lesions/Kimmelstiel-wilson
Stage 4- Advanced glomerulosclerosis
- What is amyloidosis?
- What are the forms that effect the kidney?
- Amyloidosis is a rare condition that is caused by the build up of amyloid in the body which can be deposited in any organ. Amyloid is a an extraceullular proteinaceous material exhibiting beta-sheet structure
- Commonest forms in the kidney are:
- AA- Derived from serum amyloid associated protein (SAA), and acute phase protein. Patients tend to have a chronic inflammatory state
- AL - derived from immunogloblin light chains, 80% of patients have multiple myeloma
What isolated urinary abnormalities can cause microscopic haematuria?
- Thin basement membranes
- IgA nephropathy
What is Thin Basement Membranes disorder?
- Thin basement membranes is a hereditary defect in Type 4 collagen synthesis, causing basement membranes to be <250nm thick
- Haematuria is the only consequence in most cases
What is Alport’s syndrome?
Alport’s syndrome is a genetic condition associated with progressive loss of kidney function, deafness and ocular disease.
X-linked dominant mutation affecting alpha5 subunit
Second most common genetic cause of end-stage kidney failure, after PKD.
Describe IgA Nephropathy
- Commonest cause of glomerulonephritis
- IgA predominant mesangial immune complex deposition
- 30% develop end-stage renal failure
- Aetiology not fully understood but secondary forms observed in liver, bowel and skin. Can be seen with HSP
- Describe Chronic kidney disease and associated conditions
- What GFR ml/min denotes end stage renal failure
- What are the most common causes?
- Can be caused by a range of diseases e.g. diabetes
- Association with ischaemic heart disease - hypertension, hyperlipidemia, calcification of blood vessels
- Association with calcium and phosphate metabolic derangement - hyperparathyroidism, osteomalacia and osteoporosis
- <15ml/min
- Diabetes, glomerulonephritis and PKD
Describe hypertensive nephropathy pathophysiology
Narrowing of arteries leading to scarring and ischaemia of glomeruli. Hypertension in glomeruli leading to altered haemodynamic environment, stress and segmental scarring
All this leads to reduced kidney function
Describe SLE and how it can affect the kidneys
- SLE is a systemic autoimmune disease that affects kidney, skin, joints, heart, serosal surfaces and CNS
- Deposition of immune complexes in the kidney is common
- Antinuclear and anti-dsDNA antibodies are typical - antibodies are directed at a broad range of intracellular and extracellular antigens
- Depending on the site, speed and intensity of immune complexes deposition, may present as:
- Acute renal failure, nephrotic syndrome, isolated urinary abnormality or CKD
