Renal &

Electrolytes
physiology

MRCS In Capsules

Dr. Abo Omar

 Renal Physiology
Overview

• Each nephron is supplied with blood from an

afferent arteriole that opens onto the
glomerular capillary bed.
• Blood then flows to an efferent arteriole,
supplying the peritubular capillaries and
medullary vasa recta.
• The kidney receives up to 25% of resting COP

Control of blood flow

• The kidney is able to autoregulate its blood flow

between systolic pressures of 80 - 180 mmHg so there is little variation in renal blood
flow.
• This is achieved by myogenic control of arteriolar tone, both sympathetic input and
hormonal signals (e.g. renin) are responsible.

Glomerular structure and function

• The basement membrane has pores that will allow free diffusion of smaller solutes,
larger negatively charged molecules such as albumin are unable to cross.
• In clinical practice creatinine is used because it is subjected to very little proximal
tubular secretion.
• Although subject to variability, the typical GFR is 125ml per minute.
• Glomerular filtration rate = Total volume of plasma per unit time leaving the capillaries
and entering the bowman's capsule

Substances used to measure GFR have the following features

1. Inert
2. Free filtration from the plasma at the glomerulus (not protein bound)
3. Not absorbed or secreted at the tubules
4. Plasma concentration constant during urine collection
Examples: inulin, creatinine

NB: GFR is measured by inulin & creatinine

• In clinical practice creatinine is used
• In experimental practice inulin is used
• The most accurate is inulin

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 urine concentration (mmol/l) x urine volume (ml/min)
GFR = --------------------------------------------------------------------------
plasma concentration (mmol/l)

• The clearance of a substance is dependent not only on its diffusivity across the
basement membrane but also subsequent tubular secretion and / or reabsorption.
• So glucose which is freely filtered across the basement membrane is usually reabsorbed
from tubules giving a clearance of zero.

Tubular function

• Reabsorption and secretion of substances occurs in the tubules.

• In the proximal tubule

✓ glucose, amino acids and phosphate are co-transported with sodium across the
semi permeable membrane.
✓ Mannitol, Carbonic anhydrase inhibitors
✓ 2/3 of filtered water is reabsorbed in the proximal tubules.
✓ PTH → decrease phosphate & increase ca reabsorption

• paraaminohippuric acid (PAHA) is cleared with a single passage through the kidneys
and this is why it is used to measure renal plasma flow.
• In the distal convoluted tubule: thiazide acts in it

Loop of Henle
• Frusemide acts in ALLH
• The thin ascending limb is impermeable to water & permeable to solutes
• In the thick ascending limb the reabsorption of sodium and chloride ions occurs by both
facilitated and passive diffusion pathways.
• The descending limb is permeable to water but impermeable to solutes.

In collecting duct:

- Spironolactone
- ADH
- Aldosterone

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 Diuretic agents

Site of action Diuretic

Ascending limb of loop of Henle Frusemide

Distal tubule and connecting segment Thiazides

Cortical collecting tubule Spironolactone

syndrome of inappropriate ADH (SIADH)

Mnemonic: Syndrome of INAPPropriate ADH:

✓ In creased
✓ Na (sodium)
✓ PP (urine)

causes
Malignancy • especially small cell lung cancer
• also: pancreas, prostate
Neurological • Stroke
• subarachnoid haemorrhage
• subdural haemorrhage
• meningitis/encephalitis/abscess
Infections • tuberculosis
• pneumonia
Drugs • sulfonylureas
• SSRIs, tricyclics
• carbamazepine
• vincristine
• cyclophosphamide
Other causes • positive end-expiratory pressure (PEEP)
• porphyrias

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 Renin-angiotensin-aldosterone system

Adrenal cortex (mnemonic GFR - ACD)

• Zona glomerulosa (on outside): mineralocorticoids, mainly aldosterone

• Zona fasciculata (middle): glucocorticoids, mainly cortisol
• Zona reticularis (on inside): androgens, mainly dehydroepiandrosterone (DHEA)

Renin

• Released by JGA cells in kidney in response to reduced renal perfusion, low sodium
• Hydrolyses angiotensinogen to form angiotensin I

Factors stimulating renin secretion

• Low BP
• Hyponatraemia
• Sympathetic nerve stimulation
• Catecholamines
• Erect posture

Angiotensin

• ACE in lung converts angiotensin I → angiotensin II

• Vasoconstriction leads to raised BP
• Stimulates thirst
• Stimulates aldosterone and ADH release

Aldosterone

• Released by the zona glomerulosa in response to raised angiotensin II, potassium, and
ACTH levels
• Causes retention of Na+ in exchange for K+/H+ in distal tubule

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 Calcium homeostasis
Calcium ions are linked to a wide range of physiological processes. The largest store of bodily
calcium is contained within the skeleton. Calcium levels are primarily controlled by parathyroid
hormone, vitamin D and calcitonin.

Hormonal regulation of calcium

Hormone Actions

Parathyroid hormone (PTH) Increase calcium levels and decrease phosphate levels
Increases bone resorption
Immediate action on osteoblasts to increase ca2+ in
extracellular fluid
Osteoblasts produce a protein signaling molecule that activate
osteoclasts which cause bone resorption
Increases renal tubular reabsorption of calcium
Increases synthesis of 1,25(OH)2D (active form of vitamin D) in
the kidney which increases bowel absorption of Ca2+
Decreases renal phosphate reabsorption

1,25-dihydroxycholecalciferol Increases plasma calcium and plasma phosphate

(the active form of vitamin D) Increases renal tubular reabsorption and gut absorption of
calcium
Increases osteoclastic activity at high levels and osteoblasts at
low levels
Increases renal phosphate reabsorption

Calcitonin Secreted by C cells of thyroid

Inhibits intestinal calcium absorption
Inhibits osteoclast activity
Inhibits renal tubular absorption of calcium

Both growth hormone and thyroxine also play a small role in calcium metabolism.

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 Hypocalcaemia

The clinical history combined with parathyroid hormone levels will reveal the cause of
hypocalcaemia in the majority of cases

Causes

• Vitamin D deficiency (osteomalacia)

• Acute pancreatitis
• Chronic renal failure
• Hypoparathyroidism (e.g. post thyroid/parathyroid surgery)
• Pseudohypoparathyroidism (target cells insensitive to PTH)
• Rhabdomyolysis (initial stages)
• Magnesium deficiency (due to end organ PTH resistance)

Management: intravenous calcium gluconate, 10ml of 10% solution over 10 minutes

Hypercalcaemia
Main causes

• Malignancy (most common cause in hospital in-patients)

• Primary hyperparathyroidism (commonest cause in non hospitalised patients)

• Sarcoidosis (extrarenal synthesis of calcitriol)

• Thiazides, lithium
• Immobilisation
• Pagets disease
• Vitamin A/D toxicity
• Thyrotoxicosis
• MEN
• Milk alkali syndrome

Clinical features
✓ Stones, bones, abdominal groans, and psychic moans
✓ Decreased neuronal excitability.
✓ Sluggish reflexes, muscle weakness and constipation may occur.

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 Management of hypercalcaemia
• Free Ca is affected by pH (increased in acidosis) and plasma albumin concentration
• ECG changes include: Shortening of QT interval
• Urgent management is indicated if:

➢ Calcium > 3.5 mmol/l

➢ Reduced consciousness
➢ Severe abdominal pain
➢ Pre renal failure

Management: Intravenous fluid with 0.9% Normal saline in 24 hours

Bisphosphonates

• Prevent osteoclast attachment to bone matrix and interfere with osteoclast activity
• Inhibit bone resorption.

Drug Notes

IV Pamidronate Most potent agent

IV Zoledronate Used for malignancy associated hypercalcaemia

Calcitonin: Quickest onset of action, short duration.

Prednisolone: May be given in hypercalcaemia related to sarcoidosis, myeloma or vitamin D
intoxication.

Hypocalcemia Hypercalcemia
Signs & CATS Numb Stone – bone – Abd. Groan – psychic moan
symptoms +
- Convulsions • Neural excitability
- Arrhythmia • Muscle weakness
- Tetany • Sluggish reflexes
- Spasm & stridor • Constipation
- Numbness

ttt IV Ca gluconate - Nacl

- Bisphosphonate
- Calcitonin

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 Hyperkalaemia
• Plasma potassium levels are regulated by a number of factors including aldosterone,
acid-base balance and insulin levels.
• Metabolic acidosis is associated with hyperkalaemia as hydrogen and potassium ions
compete with each other for exchange with sodium ions across cell membranes and in
the distal tubule.
• ECG changes seen in hyperkalaemia: tall-tented T waves, small P waves, widened QRS
leading to a sinusoidal pattern and asystole

Causes of hyperkalaemia

• Acute renal failure

• Drugs*: spironolactone, heparin & ACE inhibitors, angiotensin 2 receptor blockers.
• Metabolic acidosis
• Addison's
• Tissue necrosis/rhabdomylosis: burns, trauma
• Massive blood transfusion

Foods that are high in potassium

• Salt substitutes (i.e. Contain potassium rather than sodium)

• Bananas, oranges, kiwi fruit, avocado, spinach, tomatoes

*beta-blockers interfere with potassium transport into cells and can potentially cause
hyperkalaemia in renal failure patients - remember beta-agonists, e.g. Salbutamol, are
sometimes used as emergency treatment

**both unfractionated and low-molecular weight heparin can cause hyperkalaemia. This is
thought to be caused by inhibition of aldosterone secretion

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 Management of hyperkalaemia

Untreated hyperkalaemia may cause life-threatening arrhythmias. Precipitating factors should

be addressed (e.g. acute renal failure) and aggravating drugs stopped (e.g. ACE inhibitors).
Management may be categorised by the aims of treatment

Stabilisation of the cardiac membrane: Intravenous calcium gluconate

Short-term shift in potassium from extracellular to intracellular fluid compartment

• Combined insulin/dextrose infusion

• Nebulised salbutamol

Removal of potassium from the body

• Loop diuretics
• Dialysis

Hypokalaemia
Potassium and hydrogen can be thought of as competitors. Hyperkalaemia tends to be
associated with acidosis because as potassium levels rise fewer hydrogen ions can enter the
cells

Hypokalaemia with alkalosis Hypokalaemia with acidosis

• Vomiting • Diarrhoea
• Diuretics • Renal tubular acidosis
• Cushing's syndrome • Acetazolamide
• Conn's syndrome (primary • Partially treated diabetic ketoacidosis
hyperaldosteronism)

ECG features in hypokalemia

• U waves
• Small or absent T wave
• Prolonged PR & QT interval
• ST depression
• Long interval

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 Hypokalemia Hyperkalemia
Causes • Hypokalemia with alkalosis as causes of metabolic acidosis
• Hypokalemia with acidosis +
✓ Heparin
✓ Massive blood transfusion
ECG - U wave - Tall T wave
- Absent P wave - Wide QRS
- Shallow T wave - Small P wave
- ST segment depression
- Prolonged PR & QT interval
ttt B-agonist - IV Ca gluconate
never to use B-blocker

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 Hypomagnasaemia

Cause of low magnesium

• Diuretics
• Total parenteral nutrition
• Diarrhoea
• Alcohol
• Hypokalaemia, hypocalcaemia

Features

• Paraesthesia
• Tetany
• Seizures
• Arrhythmias
• Decreased PTH secretion → hypocalcaemia
• ECG features similar to those of hypokalaemia
• Exacerbates digoxin toxicity

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 Hyponatraemia

This is commonly tested in the MRCS (despite most surgeons automatically seeking medical
advice if this occurs!). The most common cause in surgery is the over administration of 5%
dextrose.

Hyponatraemia may be caused by water excess or sodium depletion. Causes of

pseudohyponatraemia include hyperlipidaemia (increase in serum volume) or a taking blood
from a drip arm. Urinary sodium and osmolarity levels aid making a diagnosis.

Classification
Urinary sodium > Sodium depletion, renal loss
20 mmol/l
• Diuretics (thiazides)
• Addison's
• Diuretic stage of renal failure

Urinary sodium < Sodium depletion, extra-renal loss

20 mmol/l
• Diarrhoea, vomiting, sweating
• Burns, adenoma of rectum (if villous lesion and large)

Management
Acute hyponatraemia with Na <120: immediate therapy. Central Pontine Myelinolisis, may
occur from overly rapid correction of serum sodium.
Aim to correct until the Na is > 125 at a rate of 1 mEq/h. Normal saline with frusemide is an
alternative method.

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 Hyperuricaemia
• Increased levels of uric acid may be seen secondary to either increased cell turnover or
reduced renal excretion of uric acid. Hyperuricaemia may be found in asymptomatic
patients who have not experienced attacks of gout
• Hyperuricaemia may be associated with hyperlipidaemia and hypertension. It may also
be seen in conjunction with the metabolic syndrome

Increased synthesis

• Lesch-Nyhan disease
• Myeloproliferative disorders
• Diet rich in purines
• Exercise
• Psoriasis
• Cytotoxics

Decreased excretion

• Drugs: low-dose aspirin, diuretics, pyrazinamide

• Pre-eclampsia
• Alcohol
• Renal failure
• Lead

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 Starling equation
GFR = Kf [(PGC - PBS) – (πGC - πBS) ]
Kf = filtration coefficient of the glomerular capillaries
PGC = glomerular capillary hydrostatic pressure
increased by dilation of afferent arteriole or constriction of efferent arteriole
PBS = Bowman space hydrostatic pressure
increased by constriction of the ureters
πGC = glomerular capillary oncotic pressure
increased by increases in protein concentration
πBS = Bowman space oncotic pressure
zero (only a small amount of protein is normally filtered)
- the net ultrafiltration pressure favors movement of fluid out of capillary --->
Filtration is favored in glomerular capillaries

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