renal and endocrine pathology

Question 1

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)

Answer 1

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.

Question 2

What pathological processes can cause an AKI/Acute Tubular Injury? Please given
an example of each.

Answer 2

● 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

Question 3

How does urine output change following Acute Kidney Injury?

Answer 3

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.

Question 4

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)

Answer 4

● 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

Question 5

What are the clinical features of obstruction

Answer 5

● 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

Question 6

What are the possible clinical sequelae of urinary tract obstruction?

Answer 6

*Infection
● Stone formation
●Atrophy/hydronephrosis/obstructive uropathy
● Renal failure and the complications of this

Question 7

Describe the progression of effects of unrelieved obstruction of a ureter

Answer 7

● 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

Question 8

Urolithiasis (Stones)
What are the main types of renal calculi?

Answer 8

● Calcium oxalate and phosphate stones (70%)
● Struvite or triple stone (Magnesium, ammonium, phosphate) (15-20%)
● Uric acid stones (5-10%)
● Cysteine (1-2%)

Question 9

What conditions favour stone formation?

Answer 9

● Increased concentration of stone constituents, changes in urinary pH, decreased
urine volume, bacteria

Question 10

What are the potential complications of ureteric calculi?

Answer 10

● Pain
● Haematuria
● Infection
● Obstructive renal impairment

Question 11

4. Post Strep Glomerulonephritis
   Describe the aetiology and pathogenesis of post strep glomerulonephritis

Answer 11

● 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

Question 12

Describe the clinical features of Post Strep GN in children

Answer 12

● 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.

Question 13

How does the clinical course differ in adults?

Answer 13

● 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

Question 14

5. Nephrotic Syndrome
   What are the manifestations of nephrotic syndrome?

Answer 14

● Massive proteinuria
● Hypoalbuminaemia - with plasma albumin levels less than 30g/mL
● Generalised oedema
● Hyperlipidaemia and lipiduria

Question 15

What are the mechanisms responsible for proteinuria?

Answer 15

Derangement of glomerular capillary walls resulting in increased permeability to plasma
proteins. Structural damage and/or physiochemical alterations lead to massive
proteinuria

Question 16

What are the mechanisms underlying the hypoalbuminaemia?

Answer 16

● 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

Question 17

What are the mechanisms underlying the Hyperlipidaemia and lipiduria

Answer 17

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.

Question 18

What are the underlying causes of nephrotic syndrome?

Answer 18

● 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

Question 19

6. 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?

Answer 19

● 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

Question 20

Describe the clinical course of pre-eclampsia

Answer 20

● 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

Question 21

Describe the morphological changes that may be seen in the placenta in
pre-ecclampsia

Answer 21

● Placental infarcts
● Retroplacental haematomas
● Villous ischaemia
Note: (there are others but you just need 3 to pass so we picked these 3)

Question 22

Diabetes
What are some of the principal complications of diabetes mellitus?

Answer 22

● 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.

Question 23

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)

Answer 23

● 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

Question 24

8. Type 1 Diabetes and DKA
   What is the typical pattern of onset of T1DM?

Answer 24

● Genetic predisposition
● Precipitating event i.e. intercurrent illness
● Autoimmune destruction if islet cells
● Subclinical then leading to overt DM

Question 25

What environmental factors may contribute to the development of T1DM?

Answer 25

Infections - Group B coxsackie viruses, mumps, measles, CMV, rubella, EBV)
These may induce tissue damage and inflammation leading to release of B cell antigens,
OR the viruses can produce antigens that mimic self antigens leading to the immune
response cross reacting with self tissue

Question 26

How does genetic susceptibility contribute to the development of T1DM?

Answer 26

There is a complex pattern of genetic associations which have been mapped to at least
20 loci.
Most important is the Class II MHC (HLA) locus which is responsible for 50% of total
genetic susceptibility. Located on chromosome 6.
95% of white people with T1DM have one or more mutations at this location.
There are other non-MHC genes associated with insulin that can alter the protsin to
make it less functional or less stable or may affect expression of insulin in the thymus,
leading to altered selection of insulin reactive T-cells.

Question 27

What is the pathogenesis of DKA?

Answer 27

Insulin deficiency and glucagon excess decreases the peripheral utilisation of glucose
while increasing gluconeogenesis leading to severe hyperglycaemia
Hyperglycaemia causes osmotic diuresis and dehydration
Insulin deficiency increases lipolysis and free-fatty-acid production, which are converted
to ketone bodies by the liver. If the rate of ketone bodies production exceeds rate of
utilisation by peripheral tissues then it leads to ketonaemia and ketonuria
Decreased urinary excretion of ketones leads to systemic metabolic ketoacidosis

Question 28

T2DM
What is the pathogenesis of T2DM?

Answer 28

Begins with insulin resistance, resulting in a decreased ability of the peripheral tissues to
respond to secreted insulin . This occurs secondary to genetic predisposing factors and
other metabolic factors.
There is both qualitative and quantitative beta cell dysfunction which manifests as
inadequate insulin secretion in the face of insulin resistance and hyperglycaemia.
Initially, beta cell hyperplasia maintains normoglycaemia with higher levels of insulin
secretion but then failure of this mechanism results in impaired glucose tolerance and
then diabetes.

Question 29

What is the genetic component with regards to T2DM?

Answer 29

Not HLA linked but there is a collection of multiple genetic defects that have been
identified. The rates of T2DM in identical twins approached 80%,

Question 30

What are the main adverse effects of severe sustained hyperglycaemia?

Answer 30

Osmotic diuresis - leads to hypovlaemia and increases risk of thrombosis
Electrolyte losses - Na, K, PO4
Hyperosmolarity - leading to changes in conscious state

Question 31

. Thyroid Stuff
Graves disease
What are the characteristic clinical findings in Grave’s disease?

Answer 31

● Clinical hyperfunction of thyroid
● Thyroid gland enlargement
● Infiltrative ophthalmopathy
● Infiltrative dermopathy

Question 32

What is the pathogenesis?

Answer 32

● Autoimmune mechanisms involving a variety of antibodies
● Auto-antibodies to TSH receptors
● IgG mimics of TSH which cause stimulation of the thyroid gland production

Question 33

What is thyrotoxicosis?

Answer 33

Hypermetabolic state caused by elevated circulating levels of T3 and T4

Question 34

What are the clinical features of thyrotoxicosis?

Answer 34

● Cardiac - tachycardia, dysrhythmias, cardiac failure
● Neuromuscular - tremor, proximal myopathy
● Ocular - wide staring gaze, lid lag, proptosis
● CNS - anxiety, emotional lability, insomnia
● Skin - warm, flushed, sweating
● Heat intolerance
● Thyroid storm - fever, tachycardia, arrhythmia, may be fatal unless treated
promptly

Question 35

1. Pituitary
   How are pituitary adenomas classified?

Answer 35

Classification is based on hormone cell type
● Prolactin
● Growth hormone
● TSH
● ACTH
● Gonadotroph
● Can also be described as mixed, hormone positive or hormone negative.

Question 36

What clinical syndromes may they produce?

Answer 36

● Prolactinoma: amenorrhoea, galactorrhoea, loss of libiao, infertility
● Somatotroph (GH): acromegaly
● ACTH: Cushing’s Syndrome
● Gonadotroph: local effects from tumour i.e. headaches, visual impairment,
diplopia, pituitary apoplexy plus hypogonadism - amenorrhoea, loss of libido and
lethargy