Proximal Convoluted Tubule Active Reabsorption –Nutrients (glucose, amino acids, Vitamins) –Ions (K +, Na +, Cl -, Ca 2+ ) –Small plasma proteins –Some urea and uric acid ~70% of Filtrate is reabsorbed in PCT Question: How are these Reabsorbed?

Reabsorption of Na + : First – simple diffusion: Then – 1 o active transport: Na + is Actively Reabsorbed:

Na + linked 2 o Active Transport Symport with: –Glucose –Amino acids –Ions (e.g., Ca 2+ )

Passive Transport of Water: –As Na + pumped out, H 2 O follows by osmosis. (passive) Transcytosis of Proteins: – Small proteins can get into filtrate, due to size they are reabsorbed via vesicular transport. Passive Transport of Urea: –As other solutes leave lumen, [urea] higher than ECF, thus passively diffuses into ECF.

Reabsorption of Urea

Transporter Characteristics A substance can exceed renal threshold, e.g., glucosuria. –Saturation (# of carriers): –Competition: –Specificity: glucose, fructose, tyrosine, valine, etc, all have own carriers. maltose instead of glucose – takes a seat, but not transported. limited # of carriers to transport solutes back into body.

First, Na + transported out of filtrate. H 2 O Reabsorption – Loop of Henle a key site. Collecting duct also a key site for H 2 O reabsorption – (role of ADH). Osmolarity of ECF gets higher. Deeper into medulla, more H 2 O drawn out. Filtrate becomes Very concentrated!

Region is impermeable to H 2 O. Ascending Loop of Henle Thus, H 2 O can no longer leave filtrate in this region, so Osmolarity becomes lower again at start of DCT.

Active Transport into nephron tubules e.g., K +, H + and HCO 3 - Secretion – DCT a key site. Fine-tuning - eliminate unwanted items. This filtrate in tubules is destined to be urine unless reabsorbed in collecting ducts.

Reabsorption of Na + Final Modification: Collecting Ducts After collecting duct, filtrate now called urine (no longer modified). Reabsorption of H 2 O Under Endocrine Control – ADH (vasopressin)

Mictruition Reflex

Autoregulation of Renal System

Renin-Angiotensin-Aldosterone

_______________________ ______________ (inactive) (_____________) _________________________________ ___________ ____________ (activated) _____ _______________ LiverKidneys Lungs Adrenal Cortex Na + _______ H 2 O _______ Thirst StimulationVasoconstrictionReabsorption of H 2 O Kidneys (active)

Anti Diuretic Hormone (ADH) Angiotensinogen (inactive) (Vasopressin) Angiotensin Converting Enzyme (ACE) Aldosterone Angiotensin I (activated) Renin Angiotensin II LiverKidneys Lungs Adrenal Cortex Na + retention H 2 O retention Thirst StimulationVasoconstrictionReabsorption of H 2 O Kidneys (active)

Comparison of Fluids PlasmaFiltrate Urine Blood Substance (parameter) Rate pH Osmolarity Cells Na +, K + Large Pro - Small Pro - Glucose Urea Volume

Renal Failure When kidney function disrupted to the point they are unable to perform regulatory and excretory functions sufficient to maintain homeostasis. Acute – sudden onset with rapid reduction in urine formation (less than 500ml/day minimum being excreted). Chronic – slow, progressive, insidious loss of renal function. Up to 75% of function can be lost before detected.

Normal Healthy Kidney

Polycystic kidneys

Enlarged Polycystic kidneys (16 to 18 pounds combined).

1. Infectious organisms. Variety of Causes of Renal Failure: 2. Toxic agents. 3. Inflammatory immune response (allergic). - Blood borne microbes - UTI’s - lead, arsenic, pesticides, additives, medications - long-term exposure to high aspirin doses - glomerulonephritis, sepsis - e.g., after strep throat (streptoccocus)

Variety of Causes: 4. Obstruction of urine flow. 5. Insufficient renal blood flow. - Kidney stone (calcium oxalate, uric acid crystals) - Tumors - Enlarged prostate gland All create back pressure, decreasing GFR - 2 o to heart failure - Hemorrhage (e.g. shock) - Atherosclerosis Leads to inadequate Filtration pressure

1. Uremic Toxicity Potential Ramifications: 2. Metabolic Acidosis 3. Potassium (K + ) retention - Caused by retention of toxins/waste products in blood. - From inability of kidneys to secrete H +. - Inability to secrete K + (effects RMP).

4. Na +, Ca 2+ and phosphate and Imbalances 5. Loss of plasma proteins 6. Anemia - Inability of kidneys to regulate ion reabsorption and secretion. - Result of increased leakiness of glomerulus. - Inadequate erythropoiten production. 7. Depressed immune system - Increased toxic waste and acidic conditions.

Possible Treatments for Renal Failure: Dialysis Kidney Transplant Stop or Treat the Cause

Overall Processes of the Nephron