Quick Renal Notes
By Dr A McLeod


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Anatomy of Kidneys
Microanatomy of Kidneys
Enzymes made by Kidneys
Stone disease
The bladder and urethra
Urine Transport
Bladder outlet obstruction
Haematuria
Proteinuria
Nephrotic and Nephritic syndromes
Renal failure
Dialysis
Renal transplant


Anatomy of the kidney

The ureter enters the kidney at the hilum where it forms the renal pelvis (lined with transitional cells). This divides into two or three major calyces, which further divide into minor calyces. Also entering the kidney via the hilum are the renal artery and vein, nerves and lymphatics.
•    The renal arteries come directly from the descending aorta in the region of L1-L2.
•    The renal veins drain directly into the IVC.
•    Lymphatic drainage is to the para-aortic nodes.
•    Innervation is mainly via the coeliac plexus

In the kidney the blood vessels are arranged into interlobar arteries and veins that run through the medulla to the boundary of cortex and medulla where arcuate vessels run at the cortico-medullary junction to join them up.

Interlobular vessels run from the arcuate vessels to supply the cortex. It is from these arcuate vessels that the afferent artery runs into the corpsucle.

Blood leaves the corpuscle by the efferent arterioles which pass though one of two types of capillary network (peritubular in cortical nephrons, vasa recta in juxtamedullary nephrons) and into the various levels (interlobular, arcuate, interlobar) of veins.

Larger version of picture here
Renal Blood Supply




Microanatomy of the kidney

The corpuscle: Made up of a glomerulus and a capsule. The glomerulus is a ‘ball’ of capillaries that invaginates into a saucer shaped receptacle about 200 μm across, called Bowmans capsule.

The glomerulus exists to produce a protein free filtrate of blood. Fluid is filtered through three negatively charged layers (capillary endothelium, basement membrane, capsule epithelium). Molecules with a MW of 70 kDa or above, or which carry a positive charge do not penetrate this filter to a high degree.

Hydrostatic forces push fluid into the glomerular capsule while oncotic pressure and a smaller hydrostatic force oppose this. The net flow is into the capsule.

Note the narrower efferent vessel - this is what maintains the high outwards pressure.
Corpuscle

Closeup of corpuscle and histology

The Nephron: the glomerular capsule leads into the nephron. Approximately six nephrons connect to a single collecting duct. Two of these ducts become a duct of Bellini and this drains urine through the apices of the renal pyramids into the renal pelvis via the minor and major calyces.

There are about 1-1.5 million nephrons in the kidney, divided into two types – each has a renal corpuscle and a tubule. They are 5-7cm long.

85% of nephrons are cortical. The corpuscle lies in the outer cortex and there is a short loop of Henle that barely penetrates the medulla. These nephrons are responsible for most of the reabsorption that occurs within the kidney. The remaining 15% of nephrons are juxtamedullary and have their corpuscles within the inner 1/3rd of the cortex. They have long loops of Henle that reach well into the medulla. These nephrons are involved in urine concentration.

Mnemonic: Cells Not Removed - Just Clean Urine = Cortical Nephrons Reabsorb, Juxtamedullary Concentrate Urine


The blood supply for the two types of nephron is slightly different:
Renal Blood Supply

90% of blood entering the kidney perfuses the cortex and cortical nephrons while only 10% perfuses medulla and juxtamedullary glomeruli.



Enzymes produced by the kidney

Renin: Produced in granular cells contained within the tunica media of the afferent arteriole of the juxtaglomerular apparatus. This enzyme converts angiotensinogen to angiotensin I within the liver.

Erythropoitin: produced in the peritubular interstitium and inner cortex cells. Stimulates erythrocyte stem cells in the bone marrow to produce more erythrocytes.

1,alpha-hydroxylase: produced in the tubular cells. Hydroxylates 25-hydroxyvitamin D3 to 1,25 hydroxyvitamin D3. This is the active form needed for calcium uptake.



The Urinary Bladder

When empty the bladder lies in the pelvis and rests upon symphysis pubis and the pubic floor. When filled it enlarges into the abdominal cavity. The neck region is relatively immobile and is held by the puboprostatic and lateral vesicle ligaments.

The blood supply is via the superior vesicular and inferior vesicular arteries which branch from the internal iliac artery. Drainage is via the vesicular plexus and the prostatic venous plexus. Lymph flows to the para aortic node.

The wall of the bladder is yellow and contains many folds that allow it to expand in the range from 100-400 ml with very little increase in internal pressure. Capacity is much higher that this (>1 L) but sensations of fullness become pain as the bladder becomes more ful.

The ureters enter into the back of the bladder through the ureteric orifices that form two corners of the trigone (along with the urethral meatus) which is reddish in colour and lies in the base of the bladder. This is less mobile / distensible than the rest of the bladder and is more sensitive to pain.

Histologically the bladder is lined by smooth muscle in three layers commonly described as two layers of longituginal sandwiching a circular layer. In reality all three layers are helices. The bladder has an internal smooth muscle (involuntary) sphincter at the neck of the bladder. An external skeletal muscle (voluntary) sphincter lies distal to this within the urethra.



The Urethra
The Male Urethra
This is about 20 cm long and is divided into three sections:
  • The prostatic urethra is surrounded by the prostate gland and is where prostatic secretions and contents of the ejaculatory duct enter.
  • The membranous urethra is the section that passes through the pelvic floor – this is where the skeletal muscle (voluntary) sphincter is located.
  • The spongy urethra is the section travelling within the penis.

Histologically the male urethra is lined by:
  • transitional epithelium proximally
  • then pseudostratified columnar
  • with stratified squamous at the external meatus merging with the skin of the glans penis.
The muscular wall is a continuation of the wall of the bladder and its lamina propria contains many vascular channels and a few mucus-secreting glands.
The Female Urethra
This is about 4-5 cm long and is simpler as it only serves one function. There is a voluntary (skeletal muscle) sphincter along its length at the level at which it passes through the pelvic floor.

Histologically the female urethra is lined by:
  • transitional epithelium proximally
  • and stratified squamous epithelium along most of its length.
The muscular wall is a continuation of the wall of the bladder and its lamina propria contains many vascular channels and a few mucus-secreting glands.




Transport of urine

Urine is formed in the kidney and transported via the collecting ducts and ducts of Bellini to the renal pelvis – as urine collects this dilates. Action potentials are generated in the pacemaker region of the renal pelvis and these generate contractions in the ureters that help the movement of urine into the bladder through the ureteric orifices in its base.



The Nephrotic and Nephritic syndromes


These confuse many students - if you are one do not worry too much. You are not alone!

Both syndromes are caused by the formation of soluble complexes of antigens after an insufficient clearing from the immune system. The difference in the syndromes is that in nephrotic syndrome there is fixation of immune system complement and in nephritic syndrome there is not.





Mnemonic: Nephrotic = No activation of complement, Nephritic - Is activation of complement!


Nephrotic syndrome: Soluble antigen/antibody complexes are deposited within the slit pores (between opposing podocyte foot processes) or within the mesangial artery.

Damage to the glomerular basement membrane leads to an increased pore size and number. Together with a decrease in the negative charge of the basement membrane, this allows a heavy urinary protein loss (>3.5g / day). This leads to hyopalbuminaemia, which in turn leads to oedema as the oncotic force within the blood vessels (from albumin) decreases.

The loss of blood volume and pressure in the afferent glomerular arteries stimulates the release of renin. This increases levels of aldosterone and increases the retention of Na+ and water so increasing the tendency towards oedema.
Nephritic syndrome: As with nephrotic syndrome, antigen/antibody complexes are deposited within the slit pores or within the mesangial artery, but in nephritic syndrome, these complexes evoke a complement based response.

Podocyte and slit pores
Podocyte and slit pore
 
In both nephrotic and nephritic syndromes:
  • Albumin and cholesterol leak into urine
  • Oncotic pressure falls
  • Widespread oedema results
Complement activation in nephritic syndrome results in:
  • Release of histamine (mast cells and platelets)
  • Dilatation of blood vessels
  • Influx of leucocytes

Nephrotic syndrome symptoms:
  • High levels proteinuria
  • Hypoalbuminaemia
  • Oedema
  • Hypercholesterolaemia
Nephritic syndrome symptoms:
  • Lower proteinuria
  • Hypertension
  • Oedema (peri-orbital, leg, sacral)
  • Oliguria
  • Uraemia

Investigations:



Renal Stone Disease

It is estimated that 2% of the population have renal or vesicular (bladder) calculi at any one time. 50% of these will develop another stone within ten years. Males are overall twice as likely to suffer from this disease than females.

Major Causes: These are those that either decrease urine volume (dehydration), reduce the levels inhibitors of nucleation, or supersaturate (calcium, oxalate, uric acid)

Dehydration: Working in hot environments, living in hot countries

Hypercalcaemia (increased serum calcium levels)
If the GFR is normal, this invariably leads to hypercalciuria and an increased risk of stone formation.
Causes include:
•    Primary hyperparathyroidism (signalling for calcium release from bone)
•    Excess vitamin D ingestion
•    Sarcoidosis

Hypercalciuria (increased urine calcium levels)
The danger level has been reported to be >7.5 mmol. / L for men and >6.25 mmol. / L for women.
Causes include:
•    Hypercalcaemia
•    Excess calcium ingestion
•    Excessive bone resorption e.g. in disuse as in immobilised patients or from bony metastases
•    Idiopathic

Hyperoxaluria (increased oxalate levels in the urine)
Causes include:
•    GI disease such as Crohn’s
•    Excess oxalate ingestion (spinach, rhubarb, tea)
•    Calcium restriction – increases the absorption of oxalate
•    Errors in glyoxylate metabolism – more oxylate is synthesised leading to renal failure in the teens – twenties. Liver transplant corrects.

Hyperuricaemia (increased serum uric acid levels) and hyperuricocuria (increased urine uric acid levels)
•    Can be caused by idiopathic gout

Urinary tract infection (UTI)
These can result in the formation of struvite stones – often big enough to form a ‘cast’ of the collecting system – these are called staghorn calculi. Mucoprotins from the bacterium make an organic matrix upon which the stone forms.
•    The most common infectious cause is Proteus mirabilis, which hydrolyses urea to ammonium hydroxide. Ammonium ions and alkalinity favour stone formation.

Drugs
These can work in one of three ways
Promote calcium stone formation (e.g. loop diuretics, antacids, glucocorticoids)
Promote uric acid stone formation (e.g. thiazides, salicylates, allopurinol)
Drug can precipitate into stones
Calcium stones are radio-opaque and form 80% of stones. 60% contain oxalate.
Non-calcium stones are radiolucent and form the remaining 20%
•    Urate
•    Struvite
•    Cystine


Clinical signs
Most stone are asymptomatic but some cause a very intense pain. This can be constant, intermittent or colicky and may be sharp or dull. If there is an obstruction present then the pain will be made worse by either copious fluid intake or by diuretics including alcohol. Physical movement may also result in pain (and haematuria) as the stone moves.

Ureteric colic is one of the most severe pains known. It generally runs from th eflank to the iliac fossa and testis or labia. The patient will be pale, sweating and restless – changing position to try to relieve the pain. The patient may vomit and there may be haematuria.

If bladder calculi are present with a bladder bacteriuria the following will be seen: frequency, dysuria, haematuria and a severe pain if trigonitis is present.

An obstruction of the bladder neck or urethra will result in anuria and painful bladder extension.

May present as acute renal failure or acute on chronic renal failure.


The history may reveal: dehydration, excess vitamin D consumption, gouty arthritis.


Investigations:
Mid-stream urine: MC&S, U+E, Ca2+, oxalate, urate, pH (acid = urate, alk = infec.)
Bloods: creatinine, Ca2+
KUB: for stag-horn and other calculi
Spiral CT
Excretion urography
Stone analysis can help with rarer causes


Management
Stones smaller that 0.5cm usually pass on their own while those larger than 1 cm usually require further intervention (see below). Other indications for intervention include: UTI, complete obstruction / anuria, and persistent or frequent pain.
Analgesia should be given e.g. intramuscular morphine and a high fluid level and increased levels of exercise should be encouraged.

Interventions include:
•    Extracorporeal shockwave lithotripsy
•    Percutaneous (through unbroken skin) nephrolithotomy with endoscopic removal of stone.
•    Open surgery


Anatomy / Histology of the Ureters

The ureters are hollow muscular tubes between 25-35 cm long they run retroperitoneally over the posterior abdominal wall in front of the external iliac artery and down to the pelvic brim.

The ureters are divided into sections:
  • the renal pelvis
  • the abdominal ureter
  • the pelvic ureter
  • intramural ureter (that part within the wall of the bladder).
The ureters have constrictions along their length dividing these sections – these narrowings are the most natural places at which stones may get stuck producing an acute colicky pain.

This pain characteristically starts in the groin and radiates to either the scrotum in men of the labia majora in women. 

The blood supply to the ureters is as follows:
  • Renal arteries
  • Lumbar segmental
  • Gonadal
  • Common Iliac
  • Internal iliac
  • Superior vesicular arteries
Drainage is by corresponding veins and lymph nodes drain to the para aortic nodes.

Sensory innervation is via T11-L2 and S2-S4
Ureteric Constrictions



Bladder outlet obstruction

This may result in acute renal failure

Causes of bladder outlet obstruction can be divided into three categories
Physical

Urethra
  • Stricture
  • Phimosis (Narrowness of opening of prepuce, preventing it being drawn back over the glans)
Prostate
  • Benign - BPH most common cause of  outflow obstruction – 1 in 3 men over 50 has LUTS due to BPH. 
  • Malignant
  • Bladder neck
Dynamic
  • Prostate
  • Bladder neck
Sympathetic smooth muscle tone – mediated by alpha-1 receptors
Neurological
  • Upper motor neurone dis. leads to high pressure detrusor contractions and poor coordination with sphincters – detrusor sphincter dyssynergia
  • Lower motor neurone dis. (S2, 3 , 4) leads to a low detrusor pressure with a large residual urine volume.


There are two sets of symptoms that may suggest BOO:

Filling
  • Frequency
  • Nocturia
  • Urgency
  • Urge incontinence
  • Enuresis

Voiding

  • Hesitancy
  • Poor flow
  • Straining to void
  • Post micturition drbbling
  • Feeling of incomplete bladder emptying
When these are present a full exam should be made and investigations ordered:

Abdominal exam: suprapubic area for palpable bladder / suprapubic tenderness

Digital rectal exam: prostate for size, shape, consistency and abnormalities suggestive of cancer.

Immediate tests:
Bloods: U+Es inc creatinine, PSA
Urine: U+E's, dipstick, MC+S

If renal impairment suspected
Ultrasound kidneys

Others:
Urinary flow rate (noninvasive)
Urodynamics (invasive) if flow rate equivocal, problem is neurological, or if LUTS persistant or recurrent post surgery for outlet obstruction.
Treatments include:

Pharmaceuticals (for BPH)
  • Uro-selective α-blockers
  • 5-alpha reductase inhibitors (6 months to work but more effect in larger prostates)

Surgery
  • TransUrethral Resection of Prostate (TURP)
  • Balloon dilatation
  • Stents



Haematuria

Blood in the urine, either macroscopic 'frank' (visibly red or smoky urine) or microscopic (2-5 RBCs per high power field in spun urine, dependent on lab).

One mnemonic for most common causes is GOBSHITE

G Glomerulonephritis
O Others
  • Arterfactual ie not blood e.g. beetroot, rifampicin, factitious
  • Wegeners granulomatosis
B Bladder related
  • tumours of the bladder / prostate
  • tuberculosis of the bladder or prostate
  • stone / foreign body
  • cystitis: acute, radiation, chronic interstitial cystitis (Hunner's ulcer)
  • schistosomiasis
S stones
systemic e.g. sickle cell
structural lesions e.g. UPJ obstruction, polycystic kidney
H haematological
hypercalcaemia
hereditary
HSP
HUS
I infection – pylonephritis, cystitis, prostitis, urethritis
immunological  - PSGN, IgA nephropathy, endocarditis
iatrogenic – anticoagulants, cyclophosphamide drug
T trauma
TB
tumour: anywhere in urinary system e.g. kidney, bladder, prostate etc.
toxin
E Enlarged prostate
Excessive Exercise

These could also be divided into pre-renal, renal, and post-renal if you prefer to think of them that way


Investigations

Urinalysis:

Blood tests:

Imaging:

Further investigations may include:



Proteinuria

Causes of Proteinuria

Mnemonic: SNOT DUO

S Systemic e.g. CCF, diabetes mellitus, fever, effects of excessive exercise.
N Nephrotic syndrome - renal disorder: proteinuria, hypoalbuminaemia, oedema.
O Orthostatic/postural proteinuria –absent from early morning samples (usually benign)
T Tubular proteinuria - failure of tubules to reabsorb some plasma proteins  (glomeruli normal)
D Drugs - e.g. gold, other heavy metals, penicillin, NSAIDs, solvents
U Urinary system contamination: UTI, vaginal mucus, ejaculate.
O Overflow proteinuria – extra-renal causes of excess plasma proteins, overwhelm system

These could also be divided into pre-renal, renal, and post-renal if you prefer to think of them that way

PRE-RENAL
RENAL
POST-RENAL

Key History Points
About the symptoms:

About the patient:

Key Examination Points

 
Diagnosis

Next, need to determine:
 
Key Investigations


Summary of some important diseases:

Minimal Change Glomerulonephritis

IgA nephropathy

Membranous Glomerulonephritis




Acute Renal failure (ARF)

Also known as Acute Kidney Injury (AKI) or Acute Kidney Disease (AKD)

Differentials:
The principal differential diagnosis of ARF is dehydration which is important as it is easily correctable. Suggested by:
Other causes include:
Mnemonic: A Really Good Drink Does Most TOffer Some Help
As always, differentials can also be arranged into pre-renal, renal and post-renal

Pre-renal causes:

Renal causes:

Post renal causes:


Investigations:

Immediate:
Long term

Management

Have a very low threshold for immediate specialist referral if

The two most immediate aspects of management are

The overall management of a patient with acute renal failure is divided into various management objectives:



Renal replacement therapy (RRT)

This is required when the kidneys are functioning at less than 10–15%. RRT is accomplished in one of the following ways:
 
Dialysis
Kidney transplant
 
Dialysis
People with advanced chronic renal failure (CRF) who have progressed to end-stage renal disease (ESRD) usually require dialysis.
Indicators that dialysis is required include:
eGFR at most 15 and often 10 or below.
Pericarditis associated with end-atsge renal failure


Hemodialysis (HD)

There are three methods of accessing the bloodstream:

The list of potential complications is very long. Some of the more important ones are:
Common complications
  • Hypotension (20%)
  • Light-headness (25% - 55%)
  • Nausea and vomiting (15%)
  • Leg cramps (5%–20%)
  • Back pain (5%)
  • Chest pain (5%)
  • Headache (5%)
  • Itching (5%)
  • Fever, chills (rare)
Rare, Severe Complications
  • Acute anaphylaxis 
  • Acute haemolysis 
  • Air embolism 
  • Hypoxemia
Chronic Complications
  • Access problems (e.g., clotting, infection, malfunction)
  • Infection
  • Anaemia
  • Arrhythmia 


Peritoneal Dialysis
  • Peritoneal dialysis uses the peritoneal membrane
  • Dialysate is injected into the peritoneal space in the abdomen through a two-way catheter (the Tenckhoff catheter).
  • The membrane that lines the abdomen (the peritoneum) allows waste and fluid to pass from the blood into the dialysate over the course of several hours. The peritoneal dialysate, made up mostly of salts and sugar (glucose), encourages ultrafiltration through the peritoneum.
  • The dialysate is which is pumped out.
  • The cycle starts again. 

There are two types of peritoneal dialysis:
  • Continuous ambulatory peritoneal dialysis (CAPD)
    • One cycle every 4-6 hours
    • Approx two litres of fluid exchanged each cycle.
    • Person remains active and mobile except when physically changing the dialysate.
  • Continuous Cyclic Peritoneal Dialysis (CCPD)
    • The abdominal catheter is connected to the machine at bedtime.
    • Over an 8 to 12 hour night, the machine exchanges fluid four to eight times.
    • About 10 liters are exchanged during the night.
    • The fluid lasts throughout the day with some patients require a mid-day exchange.
Peritoneal Dialysis

Complications of peritoneal dialysis include the following:
 
Renal Transplant
  • Live donor (usually a relative)
  • Cadaveric donor
  • Procedure performed under general anesthesia typically taking 2 to 3 hours.
  • The failed kidneys are left in place
  • Transplantedkidney placed below them in the abdomen.
  • Blood vessels are attached to the blood vessels of the legs and the
  • ureter is attached to the bladder with a small plastic catheter.
  • Kidney usually starts to work after about a day.
  • Lifelong immunosuppressant medications needed.
    • Rise in creatinine or new proteinuria may indicate rejection.
    • Sudden rise (esp in first year) consistent with acute rejection.
    • Slow rise consistent with chronc rejection.
Kidney transplant




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Created February 2010