Kidney pathology (7.5) Flashcards
Describe the classification of renal disease using clinical and morphological descriptions
Morphological: Vascular, glomeruli, tubular/interstitial
- Compromise/damage in one morphological component will lead to damage in another (e.g. vascular compromise will lead to iscahemia of the tubules)
Clinical:
Total: Acute and chronic renal failure
Partial (may all lead to chronic renal failure): nephrotic syndrome, nephritic syndrome, haematuria and perisistant proteinuria
Compare and contrast acute and chronic kidney failure
KEY WORDS
Extra notes below - see table:
- Acute kidney disease: Nitrogenous waste products (e.g. urea) accumulate within the blood, as filtration via the nephrons is lost
- CKD: Irreversible, gradual loss which is normally due to long term conditions e.g. hypertension and diabetes. Initially asymptomatic
- Chronic kidney disease: Determined by GFR. ↓ GFR leads to ↑ nitrogenous waste (demonstrated as risin creatinine levels)
- Effects of chronic kidney disease:
THINK OF THE FUNCTIONS OF THE KIDNEY → NOW LOST
Increased Na+ and H2O levels; hyperkalaemia; uremia; ↓ EPO production; acidosis; decreased vitamin D activation → HPT
- Bone disease in chronic kidney disease: PTH is released in response to decreased serum [Ca2+]. Renal vitamin D synthesis creates negative feedback, decreasing PTH secretion which in turn decreases the reabsorption of calcium from bone.
Acute renal failure: Outline acute tubular necrosis
☆Most common cause of acute renal failure☆
Necrosis of PCT and DCT epithelium resultant of ischaemia or toxic damage within the region.
The PCT and DCT epithelium have a high metabolic demand (active processes for ion transport etc).
Ischaemia or toxic damage causes cell death. The cells are shed and block the tubules - causing oligouria, uraemia and fluid overload. This oliguric phase creates a risk of acute renal failure.
CASTS (cell debris) observed in the urine.
In recovery polyuria is seen as the necrotic cells undergo phagocytsis and the tubule is again patent. The epithelium is not yet mature enough to be functional, causing increased urine output (polyuria). Fluids and electrolytes must be replaced to prevent imbalace and infection.
Describe the pathogenesis of diseases affecting the kidney tubules and interstitium - tubulointersititial disease
Tubuloinsterstitial disease: Affecting the tubules (DCT and PCT - due to high metabolic demand) and interstitium
Commonly caused by:
- Infection (bacterial → pyelonephritis)
- Ischaemia
- Toxic damage e.g medications
- Ischamia and toxic damage ⇒ acute tubular necrosis (ATN)
Describe factors contribuing to vascular disease of the kidney
-
Hypertension: Causes ateriolosclerososis leading to ischaemia
- Reduced renal perfusion → activation of RAAS → hypertension → arteriolosclerosis of renal arteries → ischaemia in nephrons. If many damaged → chronic renal failure
Precipitates HT through RAAS but then is damaged by the hypertension created!
- Diabetes
- Renal artery stenosis via atherosclerosis (causes hypertension via RAAS activation, as kidney perfusion is decreased)
- Embolic occlusion and infarction
- Hypotension: May cause acute tubular necrosis (via poor perfusion)
- Microthrombosis
- Medications: Those which reduce renal blood flow e.g. NSAIDS, ACEi, diuretics
- RAAS activation → hypertension → renal damage
Describe the effects of diabetes on the kidney
Vascular:
- Increased susceptibilty to atheroma. Hyaline arteriolosclerosis may ensue. This is turn may cause poor glomerular perfusion. Ischaemia of the glomerulus and tubules results, leading to nephron death. Chronic kidney failure follows
Glomerular:
- Basement membrane becomes thickened and leaky (glomerular hyalinisation). Proteinuria/microalbuminuria results, creating nephrotic syndrome and ultimately chronic kidney failure.
- Mesangial sclerosis causing the mesangial cells to crush the poorly perfused glomerular capillaries
Tubules & interstitium:
- Diabetes creates increased susceptibilty to infection
- The tubules may undergo atrophy due to vascular/glomerular disease → chronic renal failure
- Acute pyelonephritis sees the collection of pus in the tubules and collecting ducts → acute renal failure
- A combination of the above leads to renal papillary failure (papillary necrosis due to vasa recta inflammation) → acute renal failure
Describe how renal disease may cause secondary hypertension (HT)
Acute/chronic kidney disorders, reno-vascular disease
Acute kidney disorders
- Can cause at least temporary hypertension
- Hypertension results from decreased urine formation and increased sodium and water retention
Chronic kidney disorders
- Hypertension is common
Reno-vascular disease: Renal stenosis
- Atherosclerotic disease of renal blood vessels → reduced renal blood flow → RAAS is activated → vasoconstriction → sodium and water retention → hypertension
Describe the normal glomerular structure and its possible responses to injury
Normal structure: Glomerular capillary epithelium, glomerular basement membrane, podocytes
Damage via vascular disease, immunological disorders, deposition of foreign material (amyloid)
Responses to injury:
- Endothelial cell proliferation (→ decreased flow and oliguria)
- Mesangial and/or matrix proliferation
- Glomerular basement membrane thickening
- Changes in podocyte processes
- Capillary necrosis (fibrinoid)
- Fibocellular crescent formation
Describe the role of immune damage in glomerular disease
- Deposition of circulating immune complexes at the basement membrane or megangium: Common
- Circulating antigen entrapment leading to Ig binding: Cause of lupus
- Anti-GBM Igs: The autoantibodies cause damage to a GBM component (alpha 3 domain). Seen in the rare Goodpasture’s syndrome
Describe patterns of glomerula disease
(‘distribution’ of disease)
Focal: Affects some glomeruli
Segmental: Affecting one area of a single glomerulus
Diffuse: Affecting all the glomeruli
Global: Affecting the whole of a glomerulus
e.g. focal segmental
Compare and contrast the morphological features and clinical manifestations of the nephrotic and nephritic syndromes
Describe the clinical classification of glomerular disease
Acute nephritic syndrome
Rapidly progressive glomerulo-nephritis
Nephrotic syndrome
Asymptomatic haematuria or proteinuria
Chronic glomerulonephritis
Describe an example of a glomerular disease in each clinical category
Describe the clinical classification and manifestations of glomerular disease including the nephrotic and nephritic syndromes
Nephritic syndrome: Description, pathophysiology, clinical manifestations, examples
Description: Proliferative, inflammatory.
Pathophysiology: Acute inflammation of the glomerulus
- Causes damage to capillary walls → red cell casts in urine
- Occlusion of the capillary lumen (due to the proliferation of cells and influx of inflammatory cells)
Clinical manifestations:
- Haematuria
- Decreased GFR → causing hypertension and oedema
- Oliguria, azotemia
Examples:
- Acute post-infectious glomerulonephritis
- SLE
Nephritic syndromes
Acute postinfectios GN (glomerulonephritis): Description, pathophysiology, aetiology, clinical manifestations, treatment
Description: Diffuse
Pathophysiology:
- As endothelial and mesangial cells swell and proliferate the lumen becomes occluded
- Neutrophils and monocytes infiltrate
- Immune complexes develop following infection (see aetiology) and are deposited in the mesangium and basement membrane
Aetiology:
- Post-strep throat infection
- Viral
- Staph.
Clinical manifestations:
- Haematuria (cola coloured)
- Mild hypertension
- Oliguria
- Proteinuria
Treatment:
- Antibiotics
- Mostly seen in children - has good prognosis
Outline nephrotic and nephritic syndromes
Description and consequences
Nephrotic = Severe damage to the GBM and mesangium → increased permeabilty and leakiness
Nephritic = Proliferation of mesangium and endothelium of glomerulus → occlusion of glomerular capillaries
Suggest possible pre-renal, renal and post-renal causes of acute kidney disease
Unilateral obstruction can be silent for a long period due to compensation from the opposite kidney.
