Lecture 8.2: Calcium Handling in the Kidney and Stone Formation Flashcards
What is the physiological role of calcium?
- Structural
- Coagulation
- Muscle contraction + regulation of
excitability - Intracellular signalling molecule
- Regulates excitability of neurones and
myocardial cells
How do we regulate our plasma calcium level? Hormones?
- Parathyroid hormone (PTH): Acts to
INCREASE plasma calcium - Vitamin D metabolites (calcitrol): Acts to
INCREASE whole body calcium - Calcitonin: Acts to DECREASE plasma
calcium
What is the physiological response to falling calcium levels? (5)
- Chief cells secrete increased PTH
release - Increased intestinal absorption
- Increased calcium reabsorption
(kidney) - Decreased phosphate reabsorption
(kidney) - Increased calcium resorption (bone)
What effect does calcitriol (1, 25 – dihydroxyvitamin D) have? (3)
- Increased intestinal absorption of
calcium and phosphate (PRIMARY) - Increased kidney reabsorption calcium
and phosphate - Facilitates resorption of calcium
What are some Hypocalcaemia Symptoms? (7)
- Neuromuscular Instability (tetany)
- Paraesthesia
- Muscle twitching
- Seizures
- Laryngospasm
- Chovtek’s Sign
- Trousseau’s Sign
Why does Hypocalcaemia cause muscle spasms?
Hypocalcaemia causes increased neuronal sodium permeability > increased excitability of neurones
What is Chovtek’s Sign?
Twitching of the muscle of facial
expression when the facial nerve is tapped
What is Trousseau’s Sign?
Spasm of the hand and forearm when a blood pressure cuff is inflated around the arm
What are causes of Hypocalcaemia?
- Hypoparathyroidism (after thyroid
surgery, autoimmune) - Vitamin D deficiency (dietary, CKD,
lack of sun)
Treatment of Hypocalcaemia?
- Vitamin D supplements
- Calcium supplements
- Treat the underlying cause
What is the physiological response to rising calcium levels? (3)
- C cells (parafollicular cells) of the
thyroid release Calcitonin - Decreased reabsorption of calcium and
phosphate in the kidneys - Inhibition of osteoclastic activity
What are some Symptoms of Hypercalcaemia? (9)
- ’Bones, stones, groans, thrones, and
psychiatric overtones’ - Bone Pain
- Renal Stones
- Abdominal Pain/Nausea/Vomiting
- Polyuria
- Confusion
- Altered Behaviour
- Fatigue
- Coma
What are causes of Hypercalcaemia? (4)
- Primary hyperparathyroidism
- Hypervitaminosis
- Malignancy
- Renal Failure
What is the Treatment for Hypercalcaemia?
- IV hydration
- Treat the underlying cause
How is calcium reabsorbed in the PCT?: Overview
Mostly via the passive, paracellular route down an (electro) chemical gradient
How is calcium reabsorbed in the PCT?: 4 Steps
1) The sodium potassium pump extrudes
sodium from the cell generating a
concentration gradient
2) Sodium is reabsorbed from the
filtrated in the lumen down the
concentration gradient (can be
coupled to glucose reabsorption,
amino acid reabsorption etc)
3) As the concentration of sodium in the
filtrate falls, water is reabsorbed
moves by osmosis thorough the
paracellular route
4) As the concentration of calcium ions
(and other ions) in the lumen starts to
increase, calcium ions follow water
through the paracellular route
How is calcium handled by different parts of the kidney? Percentages?
- PCT (65% reabsorbed)
- TAL (25% reabsorbed)
- DCT-CNT (8% reabsorbed)
What does the transcellular part (DCT-CNT) of the nephron help regulate?
Major site for regulation of calcium
excretion
How is calcium reabsorbed in the TAL?: Overview
Mostly via the passive, paracellular route down an electro(chemical) gradient
How is calcium reabsorbed in the thick ascending limb?: 5 Steps
1) NKCC pumps one Na, one K and two
Cl ions from the lumen
2) Na and Cl ions exit the cell via.
basolateral transporters
3) K re-enters the lumen of the nephron
via ROMK channels.
4) There has been a net movement of
two negative ions (Cl) and one
positive ion (Na) from the lumen,
giving the lumen a weak positive
charge
5) Calcium moves down electrochemical
gradient via the paracellular route
How is calcium reabsorbed in the DCT?: Overview
Mostly via an active, transcellular route down an (electro)chemical gradient
How is calcium reabsorbed in the DCT?: 4 Steps
1) A basolateral ATPase extrudes
calcium
2) Calcium is also exchanged for sodium
at the basolateral surface
3) This creates a concentration gradient
between the lumen and the epithelial
cell
4) Calcium moves down concentration
gradient via the TRPV channels
What are TRPV5 channels are up-regulated by? What does this mean?
- Increase in the number or density of
cell surface receptors/increase activity - PTH
- Vitamin D
How is phosphate handled by different parts of the kidney? Percentages?
- PCT (80% reabsorbed)
- DCT (5% reabsorbed)
Where is phosphate stored in the body?
90% in bones
What transporter is responsible for phosphate transport in the Kidneys?
NAPT IIa (sodium phosphate transporter)
What is the effect of Glucocorticoids on bone?
- Inhibit osteoclast activity
- Long term: inhibit osteoblast activity
and gut absorption of calcium - Important cause of osteoporosis
What is the effect of Oestrogen on bone?
- Inhibit osteoclast activity
What is a UROlithiasis?
Stones in the renal tract
What is a NEPHROlithiasis?
Stones in the kidney
What is Renal Colic?
Pain experience with renal stones
Where are renal stones most commonly found? (3)
3 natural points of narrowing of the ureter where stones are most likely to impact:
* Pelvo-ureteric junction
* At pelvic brim (where the ureters cross
the iliac vessels)
* Vesico-ureteric junction
Why do Renal Tract Stones form?: General
- Pathophysiology of stone formation is
complex and not well understood - Basic mechanism is that crystals in
supersaturated urine adhere to the
urothelium - Thus providing a ‘nidus’ for stone
growth - Dehydration
- Personal History/Family History
- Structural Abnormalities
There are several types of renal tract stones, what are they and percentage incidence? (5)
- Calcium Oxalate (80%)
- Calcium Phosphate (5-10%)
- Uric Acid (5-10%)
- Struvite (10-15%)
- Cystine (1-2%)
What is a Horseshoe Kidney?
Horseshoe kidney, also called renal fusion, is when two kidneys are fused or joined together
Why do Renal Tract Stones form?: Calcium Stones (6)
- High Urinary Calcium (e.g. due to
hyperparathyroidism) - High urinary oxalate
- Low urinary citrate
- High sodium & oxalate in diet
- High animal protein
- Low calcium in diet
Why do Renal Tract Stones form?: Uric Acid Stones (2)
- Acidic urinary pH
- Hyperuricaeamia (e.g. due to gout)
Why do Renal Tract Stones form?: Struvite Stones (magnesium ammonium
phosphate)
Urease producing organisms (Proteus/Klebsiella) —> Produce ammonium and alkaline environment
Why do Renal Tract Stones form?: Cystine Stones
Cystinuria (autosomal recessive disorder)
Ratio of Men:Women in prevalence of renal stones?
3:1
What are the clinical features of renal tract stones? (6)
- Pain is the main symptom
- Sudden onset, very severe
- Pain radiates from the flank to the
pelvis ‘loin to groin’ (referred pain) - Comes in waves (caused by peristaltic
contractions of the ureter) - Haematuria
- Urinary Urgency
- Nausea
- Vomiting
What are the complications of renal tract stones? (4)
- Severe Symptoms
- Obstruction (stone has impact in
urinary tract preventing flow of urine) - Obstruction + infection (static urine in
kidney leads to infection) - Obstruction + kidney injury
Bedside Tests for Renal Tract Stones?
- Urinalysis (haematuria)
Blood Tests for Renal Tract Stones?
- FBC
- CRP (C-Reactive Protein)
- U and Es (is there decreased renal
function?)
Imaging for Renal Tract Stones?
- CT KUB = ‘kidneys, ureter, bladder’
- US KUB in children and pregnancy
Treatment of Renal Tract Stones (8)
- NSAIDs/antiemetics
- IV fluids
- Analgesia
- Surgical treatment
- Medical expulsive therapy = alpha
antagonists - Antibiotics
- Watchful Waiting (stone <5mm)
When is it done? Surgical Management: Extracorporeal Shockwave Lithotripsy (ESWL)
If stone is <10mm
When is it done? Surgical Management: ESWL or Ureteroscopy (possible ureteric stent)
If stone is 10–20mm
When is it done? Surgical Management: Percutaneous Nephrolithotomy (PCNL)
> 20mm or Staghorn calculus
What is a Staghorn Calculus?
A staghorn calculus is the name given to a branching kidney stone (fills kidney)
When is it done? Surgical Management: Urgent Drainage with Stent or PCNL
If stone is causing infection and
obstruction
How is Extracorporeal Shockwave Lithotripsy (ESWL) performed?
- Ultrasonic shock waves are used to
fragment the stone into smaller pieces - Which the patient will hopefully pass
spontaneously - Performed in clinic with analgesia
How is a Ureteroscopy performed?
- Endoscopic removal of the stone
using devices like a laser to fragment
the stone - In theatre under anaesthetic
- Using a ureteroscope to visualse
How is a Percutaneous Nephrolithotomy (PCNL) performed?
- Used for larger stones
- Tube is placed through the skin into
the kidney - Scope is inserted into the kidney and
the stone fragmented
General Measures to prevent Renal Tract Stone formation?
- Hydration (aim for 2.5L urine per day)
- Weight Loss
- Sodium Restriction
- Protein Restriction
