1. Excretion of drug and waste products

2. Regulatoin of plasma vol and elec balance by juxtaglomerular apparatus

3. Regulatoin of Acid/Base balance by regulating HCO₃^- and H⁺ secretion

Different segmants of the nephron unit

- and their function

1. Glomerulus
• Formation of filtrate
2. PCT
• 65% filtrate reab; 40% Na reab
3. Thin descending LOH (tDL)
• H2O reab (passive)
4. Thick ascending LOH (TAL)
• 15% F reab; 35% Na reab
5. DCT
• 10 % F reab ; 10 % Na reab
6. Cortical CT
• 2-5% Na reab; K and H secretion
  
7. Medullary CT
• H2O reab (ADH control)
  

Glomerulus - none

PCT - CA - CAi

tDL - none (osmosis) - Mannitol

TAL - NKCC2 (Na-K-2Cl) - Loop diuretics

DCT - Na/Cl channel - Thiazide

CCT - Na channels - K sparing

MCT - AQP - ADH antagonists

1. Loop D = Osmotic D
2. Thiazides
3. CAi = K sparing

Carbonic Anhydrase (CA) inhibitors

Eg: Acetazolamide, Methazolamide

Action: excretion of alkaline urine

inc. excretion of NaHCO3 and K

Retention of H ions

Tx: Glaucoma (dec. fluid production)

Acute mountain sickness (acidic brain -> hypervent)

Edema w/ severe metab alk

SE: Metab acidosis, Hypokalemia, hypersens rxn

Osmotic Diuretics

eg: Mannitol

Action: Inc. diuresis with min. electrolyte loss

Tx: Cerebral oedema (dec. ICP);

Acute renal failure (maintain high urine flow)

SE: Dehydration (only water loss, no solute loss)

Loop Diuretics

* Sulphonamide derivatives

i. Furosemide (Lasix)

ii. Bumetanide

iii. Torsemide

* Phenoxyacetic acid derivatives

i. Ethacrynic acid

Action:

Inhibit Na/K/2Cl cotransporter

Potent (high-ceiling) diuretics

inc. excretion of Na, K, H, Ca

Tx:

Edema due to HF, Liv Dz or Kidney Dz

HyperCa

SE: Hypokalemia, Alkalosis (H sec), Ototoxicity, Hyperurcemia (enhanced uric acid), hypotension

Thiazides

Eg: HCTZ, chlorothalidone, indapamide

Action:

Inhibit Na/Cl Co-Transporter in DCT

Inc. Na Cl K and H excretion

Ca Reabsorption

Tx: Hypertension (First line)

SE: Hypokalemia, Hyperlipidemia, impaired glc tolerance, alkalosis (inc. H sec), hyperuricemia

K Sparing diuretics

Eg:

- Aldosterone agonists: Spironolactone

- Exchange inhibitors:Triamterene, Amiloride

Action:

- Spironolactone comp antagonist of intrac. ald receptors

- exchange inhibitors block the Na channels to inhibit Na exchange with K and H

Tx: HTN - saves K in pts taking thiazides or Loop d's

SE: Hyperkalemia, acidosis

**in male: spironolactone -> gynecomastia

ADH Antagonists

eg: Conivaptan (Lixivaptan & Tolvaptan)

Actions: Competitive ADH antag (at V2r)

Tx:

SIADH (Syndrome of inappropriate ADH Hypersecretion)

CHF

SE: Demylenation (if inc. Na corrected too quick)

Severe hyperNa

1. CAi
• Acetazolamide, methazolamide
2. Loop Diuretics
• Furosemide, bumetanide, torsemide, ethacrynic acid
3. Thiazides
• HCTZ, Chlorathalidone, indapamide

Diuretic Rx classes that can cause ACIDOSIS

- and how?

1. CAi - inc. HCO3 secretion
   
   
2. K sparing - dec. H secretion

Diuretic Rx classes that can cause ALKALOSIS

- and how?

Loop Diuretics

&

Thiazides

- they both increase H secretion

1. segments of the nephron that are not affected by the Rx inc. their Na reab
2. toatl body Na dec is picked up by Macula densa cells -> inc. Renin release
3. sense of dec. in blood vol in baroreceptors stimulate the SNS --> Beta1 receptors --> Renin relase

1. Inc the dose

2. reduce the intake of Na and Water

3. add a 2nd or 3rd diuretics

BONUS!

Cardio Question!

* What is the most common pathologic condition restuling in aneurysm of the ASCENDING AORTA?

- and what are the characteristic features?

* Cystic Medial Necrosis

- Loss of elastic tissue

- loss of smooth muscle

(important to know when recognizing difference between asc. and desc. aortic aneurysms - possible exam Q in systems/path - CVS)