renal and endocrine pathology Flashcards
Acute Kidney Injury (note - in 2019 this exact question was asked using the term
‘Acute Tubular Injury’ - which was given as the reason for the patients drop in
renal function in the clinical stem)
Acute Kidney injury is a clinico-pathological entity which involves an acute reduction in
renal function and typically associated with tubular injury. It is usually reversible.
What pathological processes can cause an AKI/Acute Tubular Injury? Please given
an example of each.
● Ischaemia due to decreased or interrupted blood flow. This can be associated
with thrombosis (HUS, TTP, DIC), hypovolaemia, microangiopathies, malignant
HTN or renal artery stenosis
● Direct toxic injury to glomeruli/tubules - myoglobin, drugs, contrast injury,
radiation
● Acute Tubulointerstitial Nephritis - IgA nephropathy, infections, hypersensitivity to
drugs, metabolic disease
● Urinary obstructions by tumour, clot, stones, prostatic hypertrophy
How does urine output change following Acute Kidney Injury?
This is highly variable but includes the following phases
● Initiation phase: decreased urine output with elevation of urea (<36hours)
● Maintenance phase: sustained decreased output (40-400mls/day), salt and water
overload, uraemia, hyperkalaemia, metabolic acidosis
● Recovery phase: increased output, hypokalaemia. Increased vulnerability to
infection during this stage which may last for months.
Urinary Tract Obstruction
What are the possible causes of urinary tract obstruction?
Can divide these into Intrinsic (coming from within the tract) or extrinsic (i.e.
outside the urinary tract)
● Intrinsic
○ Congenital -urethral valves and strictures, bladder neck obstruction,
ureteropelvic narrowing, reflux
○ Calculi
○ Internal tumours
○ Internal inflammation - urethritis, prostatitis
○ Blood clots
○ Sloughed papillae
● Extrinsic
○ Tumours - prostate, bladder, cervix, uterus
○ Retroperitoneal fibrosis
○ Direct pressure - pregnancy, uterine prolapse, cystocoele
○ Prostatic hypertrophy
○ Functional - neurogenic bladder, dysfunctional ureter or bladder
What are the clinical features of obstruction
● Pain - due to distension or symptoms of underlying process i.e. renal colic,
cystitis
● Polyuria and/or nocturia, hypertension and tubular acidosis in bilateral partial
obstruction.
● Oligo/anuria, hy
What are the possible clinical sequelae of urinary tract obstruction?
*Infection
● Stone formation
●Atrophy/hydronephrosis/obstructive uropathy
● Renal failure and the complications of this
Describe the progression of effects of unrelieved obstruction of a ureter
● Reduced GFR
● Progressive dilation of the proximal ureter, renal pelvis and calyces
(hydronephrosis)
● Renal parenchymal atrophy
● Blunting apices of the pyramids
● Interstitial inflammation leading to interstitial fibrosis
● Enlargement of the kidney
● Eventual result is a large, thin walled non-functional cystic structure
Urolithiasis (Stones)
What are the main types of renal calculi?
● Calcium oxalate and phosphate stones (70%)
● Struvite or triple stone (Magnesium, ammonium, phosphate) (15-20%)
● Uric acid stones (5-10%)
● Cysteine (1-2%)
What conditions favour stone formation?
● Increased concentration of stone constituents, changes in urinary pH, decreased
urine volume, bacteria
What are the potential complications of ureteric calculi?
● Pain
● Haematuria
● Infection
● Obstructive renal impairment
- Post Strep Glomerulonephritis
Describe the aetiology and pathogenesis of post strep glomerulonephritis
● Group A Beta-Haemolytic streptococci (90% are types 1, 4 or 12)
● Typically occurs after a pharyngeal or skin infection (impetigo)
● It is an immunologically mediated disease thought to be relating to immune
complex deposition in the glomeruli
● Characterised by granular immune deposits in the glomeruli basement
membrane leading to leakage of the glomeruli and acute proliferative
glomerulonephritis
● The streptococcal antigen is found in the glomeruli of affected kidneys
● It causes complement activation - resulting in low serum complement
● There is also an elevated anti streptococcal antibody
Describe the clinical features of Post Strep GN in children
● Usually occurs 1-4 weeks after the strep initial infection
● Symptoms include malaise, fever, nausea, oliguria and haematuria (coke
coloured urine)
● Red cell casts, proteinuria on urinalysis
● Periorbital and other oedema (less than nephrotic syndrome)
● Mild to moderate hypertension
● 95% of cases will recover in 1-3 weeks, 4% become chronic and 1% may
progress into severe acute renal failure.
How does the clinical course differ in adults?
● Adult onset has a worse prognosis.
● 60% fully recover but it is a slow resolution. The others either develop chronic GN
or rapidly progressive GN
- Nephrotic Syndrome
What are the manifestations of nephrotic syndrome?
● Massive proteinuria
● Hypoalbuminaemia - with plasma albumin levels less than 30g/mL
● Generalised oedema
● Hyperlipidaemia and lipiduria
What are the mechanisms responsible for proteinuria?
Derangement of glomerular capillary walls resulting in increased permeability to plasma
proteins. Structural damage and/or physiochemical alterations lead to massive
proteinuria
What are the mechanisms underlying the hypoalbuminaemia?
● Loss of colloid osmotic pressure
● Loss of serum albumin
● Accumulation of water and sodium in tissues
● Compensatory secretion of aldosterone (in response to hypovolaemia, increased
ADH and increased sympathetic tone) worsens the oedema
What are the mechanisms underlying the Hyperlipidaemia and lipiduria
Hyperlipidaemia is due to abnormal lipid transport, increased liver synthesis and
decreased catabolism. Lipiduria arises through a combination of increased glomerular
filtration and the increased production.
What are the underlying causes of nephrotic syndrome?
● Primary glomerular disease
○ 95% of disease in kids - mostly minimal change disease, foc al segmental
GN, membranoproliferative GN
○ 60% of disease in adults - focal segmental, membranous and a small
amount is minimal change disease
● Systemic disease - mostly adults
○ Diabetes, amyloidosis, SLE, drugs (NSAIDs), infections (malaria,
hepatitis), malignancies, others
- Pre-eclampsia (random - asked in 2008 so might not be asked but technically on
the table)
What is the pathogenesis and consequences of pre-eclampsia?
● Placental ischaemia is the key feature, leading to
● Reduction in PGI2 and PGE2
● Leads to increased renin/angiotensin II
● Combined with increased thromboxane A2 and endothelial dysfunction
● Results in systemic hypertension and DIC
Describe the clinical course of pre-eclampsia
● Usually seen after 32 weeks gestation, characterised by
● Hypertension, oedema and proteinuria
● Headache and visual disturbances are common
● Ecclampsia is characterised by seizures and coma
Describe the morphological changes that may be seen in the placenta in
pre-ecclampsia
● Placental infarcts
● Retroplacental haematomas
● Villous ischaemia
Note: (there are others but you just need 3 to pass so we picked these 3)
Diabetes
What are some of the principal complications of diabetes mellitus?
● Macrovascular changes - stroke, coronary artery disease, hypertension,
peripheral vascular disease and atherosclerosis
● Microvascular - increased permeability of capillaries to plasma proteins, cerebral
microangiopathy, nephropathy, retinopathy and peripheral neuropathy
● Pancreatic changes - loss of islet cells (in number and size), amyloid infiltration of
islets
● Renal changes - sclerosis, thickening of the basement membrane,
glomerulosclerosis
● Occular changes - haemorrhages, neovascularisation, detachment of the retina.
Glaucoma.
Outline some of the differences between type 1 and type 2 diabetes (note - some
of this is largely different in real life and there are a number more types of
diabetes now recognised but we have kept the question in just in case as it’s from
2014)
● Type 1
○ Onset in childhood, usually abrupt due to exhaustion of reserve
○ Patients often underweight
○ Decreased blood insulin
○ Circulating islet cell antibodies
○ Polyuria, polydipsia, polyphagia and ketoacidosis
○ Genetic link with T cell dysfunction that produced autoantibodies to islet
cells
● Type 2
○ Often older at diagnosis
○ Less unwell at time of diagnosis
○ Often have a high BMI
○ No antibodies to islet cells
○ Less of a genetic component
○ Characterised by insulin resistance and high levels of insulin in the blood
- Type 1 Diabetes and DKA
What is the typical pattern of onset of T1DM?
● Genetic predisposition
● Precipitating event i.e. intercurrent illness
● Autoimmune destruction if islet cells
● Subclinical then leading to overt DM
