Acid base regulation and renal failure

• Describe the normal pH os plasma

  Plasma pH is usually around 7.4

  • Acidosis < 7.35, impacts enzyme activity
  • Alkalosis > 7.45, leads to ion imbalances
• Describe the major chemical buffer in the plasma

  The formation of carbonic acid from carbon dioxide and water is a reversible reaction. Therefore, during acidosis protons combine with bicarbonate ions to form carbonic acid, which drives the reaction to the left. This is the major buffer within the extracellular fluid. Carbonic anhydrase catalyses the formation of protons and bicarbonate from carbonic acid.

  
• Describe the different types of acidosis and their causes

  Metabolic acidosis: fall in bicarbonate ions or increase in protons

  • undiagnosed diabetes- production of acidic ketones
  • renal failure- cannot excrete protons or reabsorb bicarbonate ions

  Respiratory acidosis: failure to remove carbon dioxide

  • COPD
• Describe the different types of alkalosis and their causes

  Metabolic alkalosis: occurs when there is an increase in bicarbonate or decrease in protons

  • ingestion of a lot of bicarbonate
  • vomiting decreases protons due to loss of stomach acid

  Respiratory alkalosis: Loosing too much carbon dioxide

  • hyperventilation increases breathing rate
• Describe how the kidneys alter pH

  PCT cells

  • secrete protons
  • reabsorb bicarbonate ions
  • excrete ammonium ions

  Type A intercalated cells in the collecting duct

  • secrete protons
  • reabsorb bicarbonate ions
  • excrete dihydogen phosphate ions

  Type B intercalated cells secrete bicarbonate ions during alkalosis
• Describe how the kidneys excrete protons- bicarbonate reabsorption

  This occurs in the PCT. Carbonic anhydrase II (intracellular) and IV (extracellular) catalyse the formation of bicarbonate ions, which cab be reabsorbed with sodium ions. This allows protons to be excreted via Na+ H+ exchangers on the apical membrane. Bicarbonate ions can also combine with protons in the filtrate to form water and carbon dioxide. Carbon dioxide can then be reabsorbed via some aquaporin channels and water is excreted.

  
• Describe proton excretion in the kidneys- phosphate buffering

  Phosphate buffering occurs in the PCT, DCT and CD. In the filtrate disodium hydrogen phosphate can easily free up protons or protons can combine with sodium hydrogen phosphate ions to be excreted.

  
• Describe how the kidneys excrete protons- ammonium buffering

  This occurs in the PCT or CD. Amino acids such as glutamine are metabolised to produce bicarbonate ions and ammonia. These bicarbonate ions can be reabsorbed and ammonia can move into the filtrate to mop up any free protons and produce ammonium ions. These ions are impermeable to the apical membrane and therefore are excreted.

  
• Describe diseases that are linked with increased risk of kidney disease

  • Diabetes: single largest cause of renal failure
  • excess blood sugar decreases elasticity of blood vessels, leading to narrowing and reduced blood flow and damage to large and small renal blood vessels, resulting in ischaemia and cell death.
  • Hypertension: leads to damage to nephron glomeruli and reduction in filtration
  • Kidney cancer
• Describe the causes of acute kidney failure

  Acute kidney failure is characterised by a sudden loss of renal function and is most common among hospitalised patients. There are a variety of causes, including:

  • extremely low blood pressure, e.g., trauma
  • blockage of renal blood supply
  • toxic injury, e.g., alcohol or drugs
  • ureter or bladder obstruction, e.g., gall stones
• What is urinalysis and how can it be used to detect defects in kidney function?

  This is a test used to detect a wide variety of disorders. It can be used to detect proteinuria, which is a sensitive early marker of kidney damage. This is usually measured by measuring albumin levels, which is the most abundant protein in the urine. Clinical proteinuria is defined as >300mg per day.
• Describe the cardiovascular effects of renal failure

  • Inability to control fluid levels results in an increased ECV, resulting in hypertension, which escalates renal problems
  • Increased water and sodium ion retention leads to disruption of ion balance and oedema in peripheral tissues and lungs, leading to breathing problems
• Describe respiratory effects of renal failure

  • Metabolic acidosis: kidneys fail to excrete protons so respiratory system tries to compensate
  • Laboured breathing due to pulmonary oedema
• Describe effects on the nervous system of renal failure

  • Hyperkalaemia and increased toxic metabolite waste
  • Neurone depolarisation and decreased action potential conduction
  • Peripheral neuropathy
• Describe endocrine effects of renal failure

  • Insufficient erythropoietin secretion- anaemia
  • Vitamin D deficiency- bone pain
  • Renin angiotensin aldosterone disruption- hypertension
  • Disrupted regulation of sex hormones- impaired fertility
• Describe current treatment for kidney disease

  Early stage CKD patients- aim to keep BP below 130/185 mmHg

  Later stage CKD patients- aim to keep BP below 125/75 mmHg

  • Angiotensin converting enzyme (ACE) inhibitors are effective in lowering BP and providing protecting for kidneys
  • Diet- special diet to relieve kidney workload, e.g., limit the following:
  • protein, leads to urea build up
  • phosphorus, removes calcium from and weakens bones
  • sodium, tends to raise BP
• Describe haemodialysis

  This is an artificial mechanism for filtering the blood. Prior to dialysis, in the patient’s arm the vein is connected to an artery, this leads to thickening of the vein wall because otherwise it would be too fragile for the procedure. A cannula attached to the vein and artery so that blood from the arm vein is pumped into the dialysis machine and passes over selectively permeable membrane. Balanced electrolyte solution withdraws water from the blood, which is then returned to the artery.
• Describe the advantages and disadvantages of haemodialysis

  Pros: maintains patients for years

  Cons: time consuming- there times a week for 3-5 hours

  • requires a lot of travelling to and from hospital
  • does not replace red blood cells- no erythropoietin
  • poor calcium control
  • uraemia- doesn’t completely remove waste products
• Describe peritoneal dialysis

  This is when a cannula is put in the patient’s abdomen and dialysate fluid is added to the peritoneal cavity allowing the peritoneum to act as a selectively permeable dialysis membrane. Exchange occurs with the blood and then the peritoneal fluid is drained away.

  
• Describe the advantages and disadvantages of peritoneal dialysis

  Pros:

  • Changes blood composition slowly
  • Continuous ambulatory peritoneal dialysis (CAPD) can be performed at home through the day or over night

  Cons:

  • Risk of infection- peritonitis is extremely painful
  • Not suitable for patients with polycystic kidneys