Urinary 5 renal stones Flashcards
How much dietary calcium is absorbed and how is it controlled?
20-40% (25mmol), increases in growing children, pregnancy, lactation and decreases with advancing age
Under control of 1, 25-(OH)2D
Complexing calcium reduces absorption
2-5 mmol secreted back into gut
How much calcium is filtered through and reabsorbed in the kidney per day?
250mmol filtered
95-98% reabsorbed - 65% in PCT, associated with Na and water intake, 20-25% recovered in ascending limb of loop, 10% recovered in DCT under parathyroid hormone (PTH) control
24hr urinary calcium excretion <10mmol
How much calcium is excreted in the faeces and urine?
faeces - 800mg
Urine - 200mg
What forms of calcium are in the plasma?
Ionised - active but not measured 45%
Protein bound (80% o albumin) 45%
Complexed (citrates, phosphate, etc) 10%
What is the ionised calcium reference range and the total adjusted calcium ref range?
ionised: 1.1 - 1.3 mmol/L
total adjusted: 2.10 - 2.60 mmol/L
aCalcium = mCalcium + 0.02(40 - mAlbumin)
What are the major factors associated with plasma calcium homeostasis?
PTH Bone Intestine Kidney 25-OHD 1,25-(OH)2D
What are good sources of vitamin D/calciferol?
Solar UVB
Oily fish
Egg
Cereal
How is the active form of vitamin D created?
vitamin D -> 25-(OH) vit D (25-hydroxylase)
-> 1,25-(OH)2 vit D (active form)
What are the reference ranges for 25-OH vit D?
adequate 50-150 nmol/L
Severe deficiency <15nmol/L
What are the risk factors for fit D insufficiency and deficiency?
Pigmented skin
Lack of sunlight exposure or atmospheric pollution
Exclusively breast fed
Multiple, short interval pregnancies
Elderly, obese or institutionalised
Vegetarian (or other non-fish eating) diet
Malabsorption, short bowel or cholestatic liver disease
Use of anticonvulsants (induce enzymes in the liver that break down fit D) rifampicin, cholestyramine, highly active antiretroviral treatment (HAART) or glucocorticoids
Where is 1,25(OH)2D created?
Kidney
25-OHD in liver…
What are the actions of 1,25-(OH)2D on bone?
Increases the availability of calcium and phosphate via intestinal uptake
Promote osteoblast activity and maturation of osteoclast precursor cells
What are the action of 1,25-(OH)2D on the kidney?
Inhibition of renal 1 alpha hydroxyls by intestinal absorbed phosphate
Promotes synthesis of 24,25-(OH)2D
Small effect on renal calcium and phosphate reabsorption
What functions of cells and tissue does 1,25-(OH)2D regulate?
Cell differentiation and proliferation
May decrease proliferative activity of some tumour cells
inhibition of cellular growth
Stimulation of insulin secretion
Modulation of immune and haemopoietic systems
Inhibitor of renin production
What chronic diseases are associated with fit D deficiency?
Osteoporosis Osteoarthritis Falls Insulin sensitivity Pregnancy outcomes Periodontal disease Various cancers TB Hypertension
What are the actions of PTH on bone?
Aids bone remodelling by stimulation of osteoclast activity, increasing plasma calcium and phosphate
Slowly stimulate osteoblast activity
What are the actions of PTH on the kidney?
Increase calcium and magnesium reabsorption
Decrease phosphate and bicarbonate reabsorption
Stimulates conversion of 25-OHD to 1,25-(OH)2D by 1 alpha hydroxylase
What factors influence bone growth and turnover?
Calcium phosphate and magnesium metabolism
PTH and 1,25(OH)2D
Other hormones and factors e.g. Thyroid hormone, oestrogen, androgens, cortisol, insulin etc
What are the main cause of hypercalcaemia?
Primary hyperparathyroidism
Haematological malignancies
Non-haematological malignancies
Others
What are the clinical manifestations of hypercalcaemia?
GI - anorexia, nausea/vomiting, constipation, rarely acute pancreatitis
CV - hypertension, shortened QT interval on ECG, enhanced sensitivity to digoxin
Renal - polyuria and dipsia, occasional nephrocalcinosis
Central nervous system - cognitive difficulties and apathy, depression, drowsiness, coma
What are the differences between hypercalcaemia of malignancy and primary hyperparathyroidism?
Malignancy - >3.5mmol, weeks/moths, rapid increase, renal canaliculi rare, plasma PTH suppressed, decreased bone formation
Primary hyperparathyroidism: <3.5mmol/L, moths/years, slow increase, renal canaliculi common, plasma PTH raised, increased bone formation
What is the difference between primay, secondary and tertiary hyperparathyroidism?
1 and 3 raised plasma calcium, 2 low or normal
What causes hypercalcaemia of malignancy?
Parathormone-related peptides (PTHrP) - amino acid homology with N-terminal of PTH (active portion of PTH)
Cytokines eg Tumour necrosis factor, interleukin-1
Transforming growth factor alpha (TGFalpha)
Prostaglandins
How is acute hypercalcaemia managed?
General measures - hydration, loop diuretics
Specific measures - biphosphonates, calcitonin, glucocorticoids
Treat underlying condition
What is the lifetime risk for renal stone formation?
Approx 20% men and 5-10% women will develop renal stones
50% recurrnece rate within 5 yr
After 8yrs, 63% men and 18% women form additional stones
Racial differences in stone formation
What are the manifestations of renal stones?
Need not produce symptoms - incidental finding on abdominal x-rays
Haematuria
Pain and associated complications of an obstruction in the renal tract
What is the distribution of renal stones by type?
Calcium 70-80% Magnesium Ammonium Phosphate 5-20% Urate 5-10% Cystine 2-5% Rare forms <1%
What factors are involved in renal stone formation?
Low urine volume Hypercalcuria Primary hyperparathyroid Hyperoxaluria Hyperuricosuria Hypomagnesuria
What medical conditions are associated with stone formation?
Hypercalciuria Increased oxalate consumption Enteric hyperoxaluria Ileostomy Primary hyperparathyroidism Renal tubular acidosis Hyperuricaemia Urinary infection Cystinuria
When are stones formed?
Urine supersaturation with respect to calcium oxalate
At low urine pH uric acid stone formation is favoured and may promote calcium oxalate stones
What reduces the risk of stone formation?
Ionic strength reduces risk of crystals forming
Low pH reduces urine citrate by enhancing renal tubular re-absorption and reducing synthesis of citrate
What are promoters of calcium oxalate and calcium phosphate stones?
Organic matrix
Tamm-Horsfall mucoproteins
What are inhibitors of calcium oxalate and calcium phosphate stones?
Citrate Pyrophophate Clycoaminoglycans RNA fragments Acidic glycoproteins Magnesium
What is the management of renal stones?
Increased fluid intake: urine output >2L daily
Dietary restriction of oxalate and sodium for all
Consider dietary restriction of calcium and animal proteins
What would blood screening show in evaluation of someone with renal stone formers?
Ca PTH PO4 Urate U/Es and acid base status
What urine screening would be don e to evaluate a patient with renal stones?
Urinalysis: pH, sediments
Culture: urea-splitting organisms
What would a radiograph tell you about a patient with renal stones?
Type:
Radiopaque: calcium oxalate, calcium phosphate, struvite, cystine
Radiolucent: Urate, xanthine, 2 hydroxyadenine
What investigations would be carried to out to diagnose renal stones?
History Blood screen Urine screen Radiograph Biochemical stone analysis
