Renal disease and its investigation I

sophietevans
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From the 17/10/2013 Studies in the Biology of Disease lecture.

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Question Answer
The renal medulla is highly vascularised which is useful for filtration. Which injury and clinical procedure would this be dangerous for? Kidney puncture and biopsy.
Which hormone does ecstasy increase the concentration of, which increases water retention? Anti-diuretic hormone.
Which common drug decreases anti-diuretic hormone, resulting in increased water voiding? Alcohol.
What is the main functional part of the nephron? The renal corpuscle, consisting of the glomerulus and Bowman's capsule, the original of the tubular component.
What are the cell layers that the filtrate has to pass through to travel from the afferent glomerular capillaries to Bowman's capsule and the primal tubule? The endothelial cells of the afferent glomerular capillaries, the basement membrane superficial to this, and the podocytes superficial to this. Between the podocytes are mesangial cells which produce membrane matrix to support the structure.
What are the main differences between the blood composition in the afferent and efferent glomerular arterioles? The afferent glomerular arteriolar blood contains relatively high concentrations of waste products, as well as useful molecules, whereas the efferent glomerular arteriolar blood contains low concentrations of waste products, and the same concentration of useful molecules as the afferent glomerular arteriolar blood, but which have been reabsorbed.
Why does the distal tubule contain a higher concentration of mitochondria than the proximal tubule or loop of Henle? Because energy-dependent reabsorption against concentration gradients/osmotic forces occurs here in order to 'fine tune' the osmotic balance. Earlier in the tubules, solutes have a higher tendency to move back into the blood passively, or to be exchanged independently of ATP for other isosteric molecules.
True or false: kidney tissue is densely packed and highly vascularised. True!
What does the mesangium consist of? The mesangial cells and the extracellular matrix that they are laying down.
Changes in the four main components of the glomerulus are observed in disease. What are the four main components? Capillary endothelial cells, basement membrane, podocytes, and the mesangium.
Filtration of the blood occurs through which two glomerular components? Through the basement membrane of the capillaries, and the 'filtration slits' between podocytes.
If the podocytes are damaged, filtration will be... ...impeded.
Why is electron microscopy, a rare technique, necessary in investigation and diagnosis of kidney disease? Because the changes are so subtle, it would be hard to see them without a high resolution technique such as electron microscopy.
Other than providing structural support by producing extracellular matrix, what function do the mesangial cells have in the kidney? They are the specialised tissue phagocytes of the kidney which carry out necessary phagocytic functions, from removing apoptosed cell debris to immune protection.
What is a global pattern of renal disease? The disease affects the whole glomerulus uniformly.
What is a segmental pattern of renal disease? The disease affects one segment of the glomerulus, but not another.
What is a diffuse pattern of renal disease? All glomeruli in both kidneys are affected (though usually only one kidney is biopsied...).
What is a focal pattern of renal disease? The disease affects a proportion of the glomeruli, while others are unaffected.
If a global and diffuse pattern of renal disease is seen, in which all segments of all glomeruli in both kidneys are affected by the disease, what kind of condition might you think this is? A systemic condition.
What is anuria? Non-passage of urine (<50ml/day).
What is the different between glomerulonephritis and glomerulonephrosis? Generally, in glomerulonephrosis there is no inflammation (though some glomerulonephrotic conditions involve a degree of inflammation...) while glomerulonephritic conditions are primarily inflammatory.
What is the general difference between nephritic and nephrotic syndrome? Nephritic syndrome involves signs associated with inflammation of the kidney (e.g. cardinal signs), whereas nephrotic syndrome is a non-specific disorder in which the kidneys are damaged.
What is oliguria? Low output of urine (300-500 ml/day).
What is polyuria? Excessive production of urine (2.5-3L/day).
What is uraemia? High concentrations of nitrogenous compounds in the blood.
Renal disease can be classified into partial renal failure and total renal failure. What can partial renal failure be further subdivided into? What can total renal failure be further subdivided into? Partial renal failure: nephritic syndrome and nephrotic syndrome. Total renal failure: acute renal failure and chronic renal failure. Partial renal failure can lead to total renal failure.
Describe the signs of acute renal failure. The majority of the nephrons stop working suddenly. There is oliguria and frequently anuria, as well as acidosis and uraemia as filtration is impeded.
What is the main cause of acute renal failure? Glomerulonephritis.
Is acute renal failure reversible? It is often reversible if the damaging stimulus is removed, however necrosis makes regeneration impossible and so it is often dependent on the length time that the damage has been occurring.
Why is there less of a metabolic disturbance in chronic total renal failure than in acute total renal failure? Because the body adapts over time to the biochemical change as chronic total renal failure is a progressive destructive condition which results in progressive loss of function over time. However, in acute total renal failure, the body does not have time to adapt and the evidence is in the blood, including uraemia. Polyuria is seen rather than oliguria/anuria.
Name three potential causes of chronic total renal failure. Vascular disease, glomerulonephritis, and diabetes.
Why is chronic renal failure not reversible? Because the nephrons have been destroyed. If ALL the nephrons have been destroyed, the condition is called 'end stage' kidney disease, and dialysis and preferably transplantation are necessary.
Which two of the main components of the glomerulus does nephrotic syndrome usually involve at least one of? The glomerular basement membrane and/or the mesangium. SOME nephrotic syndromes involve podocytes.
Given that the glomerular basement membrane is one of the key components involved in filtration and it is also one of the components most likely to be damaged in nephrotic syndromes, whereas nephritic syndromes are usually associated with proliferative changes, what is likely to be seen in the blood/urine in nephrotic syndrome that is not seen in nephritic syndromes? There is a loss of selective retention of proteins in the blood as a result of loss of glomerular basement membrane integrity. As a result, proteinuria and sometimes haematuria are seen, as well as hypoalbuminaemia leading to oedema (as plasma moves from low to high water potential).
Nephrotic syndromes can be split into primary and secondary disease categories. What are two primary nephrotic syndromes? Name a secondary nephrotic syndrome. Primary - minimal change disease (difficult to spot...), and focal segmental glomerulosclerosis. Secondary - membranous nephropathy (sometimes referred to as membranous glomerulonephritis, though it is a nephrotic syndrome).
What is the difference between a sign and a symptom? A sign is what the patient tells you, whereas a symptom is what the clinician sees.
What are the typical signs of nephrotic syndrome? Weight gain, fatigue, foamy urine (as it is proteinaceous), loss of appetite, and obvious oedema.
What are the symptoms of nephrotic syndrome? Proteinuria, hyperlipidaemia/hypercholesterolaemia, hypoalbuminaemia, and obvious oedema (usually in the legs/feet/ankles, less often in the hands or face).
Minimal change disease is responsible for ~20% of adult nephrotic syndrome cases, but what age group is minimal change disease most common in? Young children.
As the name suggests, minimal change disease is difficult to diagnose as there are very few changes in the glomeruli. As a result, electron microscopy is required to analyse the renal tissue. What is seen using electron microscopy? Loss of pedicels of the podocytes, resulting in less filtration, as well as appearance of microvilli and vacuolation of podocytes.
The aetiology of minimal change disease is not when understood, but which two factors are implicated? Epstein-Barr virus infection, and food allergies.
What general class of drug is used in the treatment of minimal change disease? Immunosuppressants.
What is focal segmental glomerulosclerosis characterised by? Sclerosis/scarring of segments of the glomeruli in a proportion of the glomeruli of the kidneys.
How is the immune system involved in focal segmental glomerulosclerosis? Antibody-antigen complexes from infection circulate in the blood and will bind to the basement membrane/capillary in the glomerulus and block them. This results in inflammation. Sometimes, the immune complexes form within the kidney.
What percentage of nephrotic syndrome cases are caused by focal segmental glomerulosclerosis in children? What is the different in adults? ~10% in children, but a higher proportion in adults.
Histologically/immunohistologically, how is focal segmental glomerulosclerosis usually indicated? Heavy periodic acid Schiff (PAS) staining in the sclerotic segment, as well as IgM and C3 (complement) found here.
What renal disease pattern does membranous nephropathy (or membranous glomerulonephritis) have? Global and diffuse - immune complexes are deposited in the glomerular basement membrane of all segments of all glomeruli.
What is membranous nephropathy characterised by? Deposits of immune complexes in the glomerular basement membrane in a global + diffuse pattern.
Is membranous nephropathy mainly seen in adults or children? Adults, as a cause of nephrotic syndrome.
Membranous nephropathy can lead to chronic renal failure over many years in what percentage of patients? ~50%
In membranous nephropathy, where do the immune complexes form? In the basement membrane of glomeruli, rather than at a distal site and then travelling via the circulation to the glomeruli. They tend to be IgG immune complexes.
Describe what happens at the glomerular basement membrane in membranous nephropathy. Sub-epithelial immune complexes (mainly IgG) form in the glomeruli, and extra basement membrane and mesangium is laid down as the body tries to replace what it sees as damage (proliferative). Next, the immune complexes are removed, leaving a gap in the newly thickened basement membrane which results in abnormal filtration/permeability of the glomerular basement membrane.
List some causes of membranous nephropathy. Infection (e.g. malaria, syphilis, hepatitis B); drugs (e.g. penicillamine, heroin); or even tumours such as lung cancer or lymphoma.
Is membranous nephropathy treatable? Where there is a recognised cause, successful treatment of that cause can lead to remission.
There are five patterns of response of glomeruli to damage. What are these? Endothelial and mesangial cell proliferation (seen in nephritis syndromes), basement membrane thickening (generally seen in nephrotic syndromes), capillary wall necrosis, and crescent formation.
Endothelial cell proliferation as a glomerular response to damage results in occlusion of the renal capillaries, and reduce flow through the glomeruli. What is seen in the blood/urine? Oliguria and uraemia.
Basement membrane thickening as a glomerular response to damage may be a result of immune complexes, or...? Amyloid protein - misfolded proteins form beta-pleated sheets which are non-functional but hard to break down so they accumulate in the tissue and prevent organ function.
What can cause capillary wall necrosis (which is usually fibrinoid) as a glomerular response to damage? Necrotising vasculitis or malignant hypertension.
What occurs in crescent formation as a glomerular response to damage? There is proliferation of epithelial cells as a reaction to glomerular capillary damage - the proliferative changes result from cytokine/growth factor presence in inflammation.
In mesangial cell proliferation as a glomerular response to damage, what antibody is formed? Mesangial IgA is formed.
Does type II membranoproliferative glomerulonephritis cause nephrotic or nephritic syndrome? It causes nephritic syndrome, although membranous nephropathy causes nephrotic syndrome, despite also resulting in a thickened basement membrane.
Describe the process of crescent formation as a glomerular response to damage. Crescent formation is a reaction to severe glomerular damage, and characterises rapidly progressive disease. Serum proteins and fibrin in Bowman's capsule cause overgrowth of the epithelial lining, as exposing the epithelium to growth factors and cytokines that it is not used to stimulates proliferation. As the 'crescent' of the overgrowing Bowman's capsule enlarges, it compresses the glomerular 'tuft', which shrivels and becomes non-functional. This is difficult to diagnose as the glomeruli are crushed and so they cannot be distinguished histologically - unaffected glomeruli must be examined in order to determine the disease type. Large numbers indicates a poor prognosis - usually rapid progression to renal failure.
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