What are the major homeostatic functions of the kidney? 
1. Regulation of water and electrolyte balance 2. Endocrine functions 3. Excretion of endogenous waste 4. Excretion of exogenous compounds
What is the major site of elimination and excretion in the kidney? What else is it majorly involved in?
The Nephron Regulation of electrolytes and water
At what stage is the blood filtered?
The preglomerular capillaries
Draw a rough diagram of the kidney nephron from the glomerulus to the collecting ducts. Label the major sites of filtration, secretion and reabsorption.
Where is the majority of water and salt reabsorbed (60-70)
The proximal tubule
What are the three different types of therapeutic actions on the kidney? 
1. Diuretics (affect reabsorption and secretion) 2. Affect urine pH (eg. bicarbonate) 3. Altering secretion of organic molecules (Eg. Probenecid) used in gout but masks secretion of several organic compounds (banned in sports)
What are the diuretics?
Drugs that decrease sodium and chloride reabsorption (means an increase in excretion of NaCl and a secondary increased excretion of water)
What are the 4 types of diuretics?
1. Loop 2. Thiazide 3. Potassium Sparing 4. Osmotic
What do loop diuretics cause? Give an example of a loop diuretic
Frusemide Most powerful and cause a torrential urine flow
What is the mechanism of action of loop diuretics?
Thick ascending loop of Henle Inhibit Na/K/2Cl transporter on luminal side Prevents overall flow of ions back into interstitium (no reabsorption)
Describe the pharmacokinetics of loop diuretics
Well absorbed (<1hr onset) Plasma protein bound: so it is stopped from being filtered (easily reaches site of action) Duration of action: 3-6 hours
What are the adverse effects of loop diuretics?
Excessive K loss H+ excretion (metabolic alkalosis) Hypovolaemia + Hypotension
What are some clinical uses of loop diuretics?
Hypertension (decreases blood volume) Decrease salt/water overloads in acute: pulmonary oedema, chronic heart failure and in chronic: liver cirrhosis or kidney failure
What do Thiazide Diuretics Do? Give an example
Are moderately powerful drugs that cause increased urine Eg. Bendrofluazide or hydrochlorothiazide (impdapamide - not true thiazide)
What is the mechanism of action of the thiazide diuretics?
Acts on the distal convolute tubule and inhibits the Na/Cl co-transporter on the luminal membrane.
Describe the pharmacokinetics of the Thiazide Diuretics
Orally active: 4-6 hour onset Excreted in the urine to get to site of action Duration: 8-12 hours
What are side effects of the thiazide diuretics?
Excessive K loss (same as loop) Build up of uric acid (can inhibit uric acid secretion) Less with the indapamide
What are the clinical uses of the thiazide diuretics?
Hypertension Severe resistant oedema (combination with loop)
Both loop and thiazide diuretics cause an excessive loss of potassium. What is done to compensate for this?
Given with a K supplement Or given a K sparing diuretic in combination or instead
What are the Potassium Sparing Diuretics?
Used in combination with the K-losing drugs and there are 2 major types with slightly different mechanisms of action They act on the collecting tubule and ducts.
Describe the two major types of K-sparing diuretics?
1. Acts on collecting tubule and ducts: aldosterone receptor antagonist - Prevents DNA binding and Na pump expression and thus reduces reabsorption of Na at that point without affecting K EG. Spirinolactone
2. Blocks luminal sodium channels in tubules and ducts EG. Triamterene and amiloride
Describe the pharmacokinetics of the K-sparing diuretics
Spirinolactone Orally active Slow onset 2 hours Short half life (minutes) but the metabolite is long (16hrs): duration 12-16 hours Amiloride Poor absorption Slow Onset 24 hr duration
What are some adverse effects of the K sparing diruetics
Hyperkalaemia Gastrointestinal upset
Give some clinical uses of the K sparing diuretics
Used in combination with loop or thiazide diuretics Heart failure Hyperaldosteronism
What are the osmotic drugs, give an example
Pharmacologically inert drugs (no binding) and are filtered without absorption Eg. Mannitol
What is the mechanism of action of the osmotic drugs?
Affects all parts that are water permeable (proximal tubule, descending loop of Henle, collecting tubules) Reduces passive water absorption with small reductions caused only (no effect on Na)
What are some clinical uses of the osmotic diuretics?
Raised intracranial and intraoccular pressures, prevention of acute renal failure
Why is the kidney susceptible to toxicity? [2 reasons]
About 20% of blood flow thus high exposure and concentrated amounts Can carry out metabolism which can generate reactive species
What are the mechanisms that kidney damage can occur from its elimination functions?
Direct or metabolite formation of reactive oxygen species Interference with calcium metabolism Protein/enzyme binding can cause inhibition of enzyme function or the initiation of the immune response
How does mercury cause toxicity to the kidney?
Directly and vasoconstriction Binds to thiol groups in proteins causing an immune response: immune glomerulonephritis Damage to mainly the proximal tubules (loss of brush border and mitochondrial changed = apoptosis)
How does Gentamicin cause toxicity to the kidney?
An antibiotic for gram negatives whose excretion is renal: causes proteinuria, reduced GRD and altered concentrating ability Acts on apical membrane of proximal tubule causing cell death
How to antineoplastic drugs cause toxicity to the kidney?
Cytotoxic agents that cause dose-limiting nephrotoxicity (proteinuria, increase blood urea, electrolyte imbalances) Highly reactive species binding to cell components to kill tumour cells and kidney cells (focal tubular necrosis)