Physiology of the kidneys

Mechanisms of Urine Formation - By three separate processes - Glomerular filtration - Tubular reabsorption - Tubular secretion

Final product is urine : waste substances, excessive water & electrolytes

Glomerular filtration
- Blood is filtrated out of glomerular capillary into Bowmans capsule - by
hydrostatic pressure

- The resulting fluid is called glomerular filtrate

- Filtration must cross 3 layers before entering the tubular system: 1. First layer glomerulus endothelium fenestrations 2. Middle layer glomerulus basement membrane 3. Third layer podocytes pedicels filtration slits

The 3 layers fenestrated endothelium, basement membrane, filtration slits filtration barrier

- Though composed of 3 layers, the membrane is 100-1000 times more permeable to water & ions compare to ordinary capillary membrane

- Content of glomerular filtrate = content of plasma except NO PROTEIN

Glomerular filtration rate (GFR)

- Definition: Amounts of filtrate formed in the capsular space each minute - Normal 70 kg man, GFR is 125 ml/min or 180 L/day - GFR blood pressure Factors affecting GFR 1. Renal autoregulation** - intrinsic mechanism 2. Sympathetic neural regulation** - extrinsic mechanism 3. Renin Angiotensin system** - extrinsic mechanism 4. Atrial natriuretic peptide hormone (ANP)*

2) Neural regulation

3. Renin Angiotensin system

Blood pressure Angiotensin I Stimulate kidney renin

Angiotensin II

Release aldosterone, increase Na+ reabsorption, water follow, increasing blood volume

Constrict arterioles GFR

Blood pressure

4. Atrial natriuretic peptide hormone

ANP is a vasodilator afferent arteriole Inhibit renin Na+ excretion, water follow

GFR

Blood volume

Blood pressure

Tubular Reabsorption
- 99% of glomerular filtrate is reabsorbed - 1% remained as urine

- Not only volume of filtrate is altered but also its composition

- Present in glomerular filtrate are water, glucose, amino acids, Na+, K+, Ca2+, Cl-, HCO3-, HPO4-, urea, uric acid, creatinine.

- Substances movement from nephron tubules back into peritubular capillary tubular reabsorption

- Reabsorption process is carry out by epithelial cells in the tubules

- Epithelial cells have tight junction to limit movement of substances

- Nutritionally important substances ; glucose & amino acid, are completely reabsorbed in proximal convoluted tubule (PCT)

- Water and many ions are reabsorbed to varying degrees in various part of nephron, hormonal dependent

- Reabsorption of substances from filtrate occurs by passive (non-energy requiring) and active (energy requiring) transport mechanisms

- Substances actively reabsorbed; glucose, amino acids, most ions

Sodium reabsorption
- There exist concentration gradient from tubule lumen (high sodium) to the interior of epithelial cell (low sodium) - There is also electrical gradient between intracellular and tubular lumen - Movement of sodium favors from filtrate into the epithelial cells - Active transport of sodium in PCT, DCT and collecting duct Na/K ATPase pump

Potassium reabsorption

- Potassium reabsorption occurs in PCT 80% reabsorbed

Water reabsorption - Sodium reabsorption also causes water movement into peritubular by osmosis - vary by hormones Others ion reabsorption - With the osmotic movement of water out of filtrate into peritubular capillary, the remaining substances in the filtrate; Cl-, HCO3-, urea, become concentrated and then move passively down their concentration gradient

Glucose reabsorption - Almost 100% reabsorption occurs in PCT - Glucose and sodium are both coupled to the same carrier protein (cotransported) - Sodium moves down its concentration gradient, but glucose moves up its concentration gradient

***

- The transport systems for glucose are carrier-specific and transportlimited; there is a transport maximum (Tm)

- When carrier become saturated and the transport system maximum is exceeded, glucose will spill into the urine glycosuria or glucosuria

Urea and uric acid reabsorption - Urea ~ 50% reabsorbed in PCT, - urea- by products of protein

Tubular Secretion
- Final composition of urine also depends on tubular secretion of substances from blood into the filtrate - Occurs in PCT, DCT, collecting duct

- Substances movement across epithelial cell by passive and active transport mechanism
- Major substances that are secreted; hydrogen and potassium ions

H+ secretion
- Important in the regulation of acid-base balance in the body - Hydrogen ion are secreted when the body fluids are too acidic - Secretion is decreased when the body fluids are not acidic K+ secretion - Potassium ions are actively reabsorbed in PCT & actively secreted in DCT & collecting duct - Active secretion is variable to ensure a constant plasma potassium level

- Plasma potassium levels is maintain around normal, - Elevated may cause cardiac arrhythmia and cardiac muscle weakness, - Low K+ levels may cause skeletal muscle weakness

Renal (Plasma) Clearance

Definition: volume of plasma that is cleared of a particular substance in a minute Why do we need to know? 1. To determine GFR, thus provide the amount of functioning renal tissue glomerular damage 2. Determine drug dosage to maintain therapeutic level high renal clearance mean high dosage (that need to be used)

- Renal clearance rate (RC) of substance in ml/min, is calculated from the equation.

RC = UV/P
U = concentration of the substance in urine (mg/mL) V = flow rate of urine formation (mL/min) P = concentration of the substance in plasma (mg/mL) - To determine whether the clearance value of substance is or , inulin RC is used as a standard.??

- Inulin is not reabsorbed, stored, secreted by the kidneyand its RC value is equal to GFR (125 mL/min). thus,

- If RC value of substance < RC inulin ; substance is partially reabsorbed.

- If RC value of substance > RC inulin ; substance is secreted into the filtrate.

- If RC value of substance is zero ; substance reabsorption is complete or the substance is not filtered.