Renal Pathology

Question 1

What do the kidneys do?

Answer 1

Filter blood to get rid of waste products
Maintain electrolyte & water balance
Secrete essential hormones

Question 2

What are the symptoms of kidney failure?

Answer 2

Tiredness and lethargy
Persistent Headaches
High Blood Pressure
Swelling in the face and / or ankles + fluid retention
Low Back Pain

Question 3

the main functioning unit of the kidney is the?

Answer 3

NEPHRON

Question 4

What are the key bits of kidney anatomy?

Answer 4

Renin (covered in CV pathology – the Renin Angiotension Aldosterone System)
secreted by the juxtaglomerular apparatus
responsible for activating angiotensin  stimulates secretion of aldosterone by adrenal cortex  acts of tubules to reabsorb sodium ions & water  maintain plasma volume & BP
The glomerulus
highly specialised capillary system & basement membrane of epithelium to create a highly selective barrier.
Collecting tubules & ducts
Reabsorption of water under control of the anti- diuretic hormone (ADH)

Question 5

What is Glomerular Filtration Rate?

Answer 5

The kidney must filter approximately 1100ml – 1200ml each minute
If this is impaired, it can have severe consequences
GFR is a test which can be done to monitor how well the kidney’s are functioning

GFR Test is recommended for people with Chronic Kidney Disease, or for those who may develop Kidney Disease due to:
Diabetes
Family History of Kidney Disease
Frequent UTIs
Heart Disease
High BP
Urinary Blockage

Question 6

how does renal failure occur?

Answer 6

Damage to one component of the nephron usually leads to damage in the other components

The kidney’s have a considerable amount of functional reserve,
but once a disease process damages a sufficient amount of nephrons to exceed the compensatory ability of those remaining,
renal failure will occur.

Question 7

What is Glomerular Diseases Vs Tubular Diseases?

Answer 7

The glomerulus ability for selective filtration is due to its specialised glomerular basement membrane
therefore, it’s ability to function is determined by the integrity of its structure.

The function of the renal tubule is mostly determined by metabolic activity of the lining epithelial cells.
tubular function is affected by diseases which causes metabolic insult to the tubule epithelial cells e.g. hypoxia or toxins.

Both glomerular and tubular function are highly dependant on adequate perfusion by blood
therefore if blood flow is disrupted, both functions are impaired.

Question 8

Two main types of partial renal failure. What are they?

Answer 8

1. NEPHRITIC SYNDROME
2. NEPHROTIC SYNDROME

Question 9

What is . NEPHRITIC SYNDROME. (partial renal failure) ?

Answer 9

as a results of disturbance of glomerular structure that involves reactive cellular proliferation.

This causes a reduced glomerular filtration rate
which leads to:
decreased urine output (oliguria)
leakage of red blood cells from damaged glomeruli (hematuria)
retention of waste products (uremia)
AND
activates the RENIN- ANGIOTENSIN SYTEM
causing fluid retention & mild hypertension

Question 10

What is 2. NEPHROTIC SYNDROME. (partial renal failure) ?

Answer 10

as a result of abnormality in the glomerular basement membrane
which means the glomerulus loses its capcity for selective retention of proteins in the blood.

This leads to:
A loss of very large amount of protein, mostly albumin, in the urine (proteinuria)
loss of protein in the blood (hypoalbuminemia)
which leads to edema
susceptibility to infections
due to low levels of immunoglobulins & complement
susceptibility to thrombosis
because of increased levels of fibrinogen in the blood
Hyperlipidaemia
due to reduced levels of serum apolipoproteins

Question 11

What is acute renal failure?

Answer 11

characterised by abrupt, widespread cessation of nephron function.
it is a form of renal failure
the majority (but not all) of the nephrons suddenly and simultaneously stop working.

Clinically, this causes:
a dramatic fall in urine production (oliguria), which can often be total fall in production (anuria)

The abrupt fall in function doesn’t allow for much metabolic compensation
therefore problems with fluid and electrolyte balance and a failure of elimination occurs rapidly.

Consequently:
increased serum potassium levels
increased metabolic acidosis
nitrogen retention with uremia

Question 12

Is acute renal failure reversible?

Answer 12

Importantly, acute renal failure is often reversible IF the damaging stimulus is removed, which allows regeneration of epithelial and / or tubule cells.
When severe necrosis occurs, recovery may not be possible.

Question 13

what is oncotic pressure?

Answer 13

blood pressure within the blood cells

Question 14

Several diseases can produce acute renal failure which can be divided into?

Answer 14

Central Perfusion Failure
Tubular & Interstitial disease
Glomerular Diseases

Question 15

What is Central Perfusion Failure?

Answer 15

e.g hypovolemic shock, sudden & profound hypotension – such as in MI (Myocardial Infarction)
Most common cause of reversible acute renal failure.
epithelial cells & tubule cells may undergo extensive necrosis , which eventually leads to failure of the entire nephron.

Question 16

What is Tubular & Interstitial disease?

Answer 16

due to hypoxia or infective damage e.g. acute pyelonephritis

Question 17

What is Glomerular Diseases?

Answer 17

immune mediated damage to glomeruli can sometimes cause acute renal failure when all glomeruli are damaged at the same time.

Question 18

What is chronic renal failure?

Answer 18

Progressive Destruction of individual nephrons over a long period of time.
usually years

As more and more nephrons become progressively irreversibly damaged
however in contrast to acute renal failure, there is opportunity for some metabolic compensation
As there are so many nephrons, even with some being slowly damaged, urea & creatine can continue to be excreted at normal levels for a long time before this is effected.

Chronic Kidney Disease can be detected at an early stage by measuring glomerular filtration rate
as for many years this can be asymptomatic.

Produces may symptoms due to the effects of:

Progressive retention of nitrogenous metabolites (especially urea), leading to:
Clouding of consciousness  that leads to eventual coma
Polyneuropathy
Gastrointestinal symptoms – gastro esophagitis & colitis
muddy brownish discoloration of the skin with severe itching

Produces many symptoms due to the effects of:

Progressive failure of tubule function, which produces abnormalities in homeostasis including:

salt & water retention  Causes HYPERTENSION
metabolic acidosis
hyperkalaemia & hyponatremia

Produces many symptoms due to the effects of:

Secondary Hyperparathyroidism & bone disease
due to excessive calcium loss in urine & failure of Vit D activation

Anaemia
due to reduced erythropoietin levels

Question 19

What are the stages of chronic renal failure?

Answer 19

Stage 1 - Normal Function
Stage 2 - Mild loss of function
Stage 3 - Moderate loss of function
Stage 4 - Severe loss of function
Stage 5 - Kidney Failure

Question 20

What are the causes of chronic renal failure?

Answer 20

Main causes:

Chronic Vascular Disease
long standing hypertension

Glomeruli Disease
glomerulonephritis
diabetic glomerular disease

Congenital Causes:
Polycystic kidney Disease

Question 21

What happens at end stage kidney disease?

Answer 21

Kidney is small and shrunken
Many years of nephron destruction, virtually all the glomeruli are converted into acellular spheres of hyaline material

these are devoid of capillaries
associated tubules are severely atrophied

Question 22

What is the link of vascular disease and the kidney?

Answer 22

Kidney function depends on a normal vascular supply
therefore, it is no surprise that hypertension & vascular disease has a great impact on renal function

Hypertension leads to ischaemic changes

Emboli leads to renal vessels occlusion, leading to infarction.

Question 23

What is Thomboemboli & the Kidney?

Answer 23

The most common cause of renal infarction is a embolus in one of the branches of the renal arteries.

Most commonly due to a thrombus formed over either:
a recent myocardial infarction
thrombus on a mitral or aortic valve prosthesis
thrombus from the left atrium of patients with atrial fibrillation.

Question 24

What is Atherosclerosis & the Kidney?

Answer 24

Generalised atherosclerosis particularly affects the aorta and the origin of the renal artery
But in severe cases, will extend into the main renal arteries and their major branches.
This can lead to renal artery stenosis which subsequently causes:
reduction of blood flow to the kidney
chronic ischemia
reduced function of nephrons
eventually end stage shrunken kidney.

Question 25

What is Hypertension & the Kidney?

Answer 25

In long standing hypertension, the following effects occur to the renal vessels which eventually leas to a reduced blood flow to the glomeruli:

Renal artery branches show thickening of the wall due to a combination of muscular hypertrophy of the media, fibroelastic intimal proliferation & elastic lamina reduction.
Afferent arterioles muscular walls become replaced by an amorphous material which is rigid & inelastic.

Thickening of the vessel wall leads to a reduction in the size of the lumen & therefore:
reduced blood flow.
Chronic progression reduction in blood flow leads to chronic ischemia
eventually leads to necrosis of nephrons
leads to reduction of GFR
Eventually sufficient numbers of nephrons are non- functioning and patients develop chronic renal failure.
this process is termed hypertensive nephrosclerosis.

this is in an important complication of long standing hypertension!

Question 26

What are Glomerular Diseases?

Answer 26

The glomerulus is the target of many disease processes which can lead to either:
temporary or permanent impairment of function

It can be damaged by:
Generalised vascular disease  hypertension
Immunological disorders
Amyloid deposits

Question 27

What is Glomerulonephritis?

Answer 27

a term used to describe the group of diseases in which the primary pathology is some sort of structural, abnormality in the glomerulus.

Most cases of glomerulonephritis are caused by another diseases such as SLE
which leads to antigen- antibody complexes forming and being deposited in the glomerulus
Damage to the glomerulus can cause scarring which can leads to associated tubule atrophy.

Glomerular diseases can affect the glomeruli in varying degrees.

This explains why some glomerular disease can cause sudden acute renal failure, whilst others only cause partial renal failure

Question 28

Glomerulonephritis: Types of Clinical Features?

Answer 28

structural changes to the glomerular basement membrane
lead to nephrotic syndrome ( increased loss of protein in urine)

glomerular damage associated with proliferation of endothelial cells
leads to nephritic syndrome (blood in urine)

Damage to both glomerular basement membrane & cell proliferation
Mixed Nephrotic / Nephritic Syndrome

Damage to glomeruli is rapid & widespread
 Acute Renal Failure

Question 29

What is Diabetes Mellitus and The Kidney ?

Answer 29

Uncontrolled Diabetes is one of the most common causes of end stage kidney disease.
particularly Type 2 due to associated vascular disease

Vascular Disease in Diabetics (uncontrolled):
Diabetics can have particularly severe atheromatous disease
which involves large, medium and small branch arteries.
Intimal thickening of atheroma leads to reduction in lumen size
leads to poor glomerular perfusion by blood
Reduced GFR
Ultimately glomerular ischaemia.
In diabetes, the kidney is particularly prone to acute bacterial infection
known as acute pyelonephritis

this affects the tubules and interstitium
this predisposed renal papillary necrosis

Question 30

What is Acute Pyelonephritis ?

Answer 30

Inflammation of the tubules & Interstitium caused by bacteria.
(usually E.Coli but can be other bacteria)

Bacteria enter in 1 of 2 ways:

Lower Urinary Tract
common causes: Diabetes pregnancy, enlarged prostate

2. Bloodstream
   Far less common, but can occur in elderly patients in septicemic states.

Symptoms

Back Pain
Fever
UTI symptoms

if untreated can lead to:
Acute renal failure, septicaemia, papillary necrosis.

Question 31

What is Obstruction?

Answer 31

Obstruction can impair drainage of urine from the kidney which causes hydronephrosis.
Obstruction can occur anywhere in the tract:
Renal Pelvis
Ureter
Bladder
Urethra

Obstruction can be either due to calculi, tumour, or extrinsic compression such as during pregnancy

Question 32

What is Renal Calculi?

Answer 32

These can form anywhere in the lower urinary tract
most commonly the bladder and pelvicalyceal system.
Formed by persistently abnormal urinary pH or increased solutes in urine.

Conditions that predispose renal calculi are:
Low fluid intake
persistent urinary tract infections
primary metabolic disturbances

4 main types:
Caclium Oxalate and phopphate calculi (most common- 80% of cases)
can be associated with inflammatory bowel disease
Magnesium Ammonium Phsosphate (15% of cases)
associated with UTIs
Uric Acid Calculi (5% of cases)
Cystine Calculi (rare – less than 1% of cases)

Question 33

What is Benign Prostatic Hyperplasia?

Answer 33

Most common disorder of the prostate
Affects almost all men over the age of 70
Found with increasing frequency & severity from the age of 45 and upwards

Clinical Presentation
Difficulty with micturition
Frequent need to urinate through the night

Symptoms are due to:
Enlarging prostate compresses the urethra
most commonly the lateral lobes of the prostate
In some cases, the posterior lobe enlarges which can greatly obstruct the bladder neck.

Prolonged prostatic obstruction can lead to marked hypertrophy of the bladder wall, and can affect retention of urine.
this increases risk of infection.

Cause is not fully understood
It is believed it may be due to androgen – oestrogen imbalance which causes prostate gland to undergo hyperplasia.

Question 34

What is prostate cancer?

Answer 34

Most common malignant tumour in men.
Tumour arises in the peripheral glands and can invade urethra
Often prostatic cancer is well established before symptoms such as difficulty wit micturition occur.
Therefore, screening to detect early stage prostate cancer is important
test for Prostate Specific Antigen (PSA)

Question 35

What is the clinical overview of the urinary system?

Answer 35

The kidneys continuously filter waste products, allow reabsorption of certain components back into the blood stream.
they filters approx. 1100- 1200ml of blood per minute known as glomerular filtration rate
Therefore, most diseases of the kidneys will be associated with abnormalities of either the blood vessel system or the epithelial lined tubule system- or both.
The kidney is particularly vulnerable to vascular disease such as:
consequences of atheroma & vessel abnormalities associated with diabetes mellitus and hypertension.
The kidneys are also sensitive to several types of immune reactions in where immune complexes are deposited on the walls of the blood vessels forming the glomerulus
this group of disorders are called the “glomerulonephritidies”
the kidneys are very metabolically active & so are extremely vulnerable to hypoxia & necrosis of epithelial cells
which is the most common cause of acute renal failure.
The urinary tract is predisposed to bacterial infection known as pyelonephritis.
Urine is a concentrated solution of solutes, which sometimes form calculi and can obstruct the urinary system.

Question 36

What is the glomerulus?

Answer 36

Part of the kidney that filters blood