Kidney Function PDF

Basic Renal Exchange Process. Water 99.2% Glucose 100% K+ Plasma- like Bulk Flow Glomerular filtration—from glomerulus to Bowman’s capsule Reabsorption—fr...

Basic Renal Exchange Process. Water 99.2% Glucose 100% K+ Plasma- like Bulk Flow Glomerular filtration—from glomerulus to Bowman’s capsule Reabsorption—from tubules to peritubular capillaries (back into blood) Secretion—from peritubular capillaries to nephron tubules Excretion—from tubules out of body Different Parts of Nephron Vary in Function. Anything filtered into kidney tubules that is not reabsorbed back into bloodstream is excreted in urine.  Proximal Tubule is the Mass Reabsorber. Unregulated! Leaky tight junctions. Brush border provides large surface area. Loaded with mitochondria to produce ATP to drive active transport- reabsorption. Also some H+ secreted INTO proximal tubule from peritubular capillaries.  Proximal Tubule Unregulated Re-absorption: Na+ ~70%, Glucose ~100%. Na+/K+ pump in basolateral membrane sends 3 Na+ out into peritubular fluid Na+ then diffuses and enters capillaries through fenestrations. New Na+ enters apical membrane (from tubular fluid) via channels and secondary active transport (Ex. Na+/Glucose symporter). In Proximal Tubule- Water Follows Solutes (Ex. Sodium, Urea). ~70% water reabsorbed.  Loop of Henle Produces Medullary Osmotic Gradient To allow Fine Control of Urine Volume (H2O) in Subsequent Collecting Duct. Fresh 150 300 700 500 Actively Pumped Ions Create 1400 Osmotic Gradient. Descending Loop of Henle: H20 flows out (concentrating tubular fluid) Ascending Loop of Henle: Na+, K+, Cl- actively pumped out (H20 can’t follow- diluting filtrate)  Distal Tubule and Collecting Ducts Regulate Reabsorption of Specific Substances (Ex. Water and Na+). Transport is highly regulated across epithelial plasma membranes, and “tight” tight junctions limit paracellular transport. Reabsorption regulated via hormones (Ex. ADH, Aldosterone). Also secretion into distal tubule occurs (Ex. K+ and H+).  H2O Re-absorption in the Collecting Duct is regulated via Antidiuretic Hormone (ADH) secreted from pituitary to conserve H2O. PKA phosphorylates Aquaporin 2 causing their insertion into apical membrane. Aquaporin 3 always in basolateral membrane. Ex. when blood volume low (or osmolarity high)- ADH release from brain (pituitary) causes aquaporin (water channel) insertion into collecting duct apical membrane. Aquaporins allow water to leave tubular fluid down concentration gradient (created by loop of Henle) back into bloodstream. Diabetes insipidus = No ADH signalling Aquaporin Insertion Causes H2O to get Re-absorbed Back into Plasma Allowing body to conserve water. No Aquaporin Aquaporin Osmotic gradient produced by Loop of Henle  Control of Urinary Water Excretion in Distal Tubule is Instrumental in Regulating Plasma volume (MAP) and Osmolarity.  Na+ Reabsorption in Distal Tubule. Na+ actively pumped across basolateral membrane via Na+/K+ ATPase. Na+ moves across apical membrane by channels or cotransport. Often coupled to K+ secretion (Regulated via aldosterone). Aldosterone Increases Sodium Re-absorption Back Into Bloodstream and K+ secretion into Distal Tubule and Collecting Ducts. Aldosterone released from adrenal cortex. Steroid hormone crosses plasma membrane and binds cytosolic receptor- Signals to increase number of Na+/K+ pumps on basolateral membrane and Na+ and K+ channels on apical membrane. Aldosterone Secretion is Regulated via the Renin/Angiotensin System. When Na+ levels drop: “Sensed” by cells in the macula densa which stimulate nearby juxtaglomerular granular cells to secrete Renin (protease). Renin “clips” angiotensinogen into angiotensin I. Angiotensin I “clipped” by ACE into Angiotensin II. Angiotensin II travels to adrenal gland to stimulate aldosterone release. Aldosterone travels through blood to cause increased Na+ reabsorption via increased pump and channel intercalation into distal tubule cell membranes. Juxtamedullary Apparatus Contains Specialized Kidney Cells that help regulate blood volume and MAP. Juxtaglomerular granular cells- secrete protease Renin- involved in Na+ reabsorption and MAP regulation.  When MAP Declines- Renin/Angiotensin System Can Kick In To Increase MAP back to Set point Level. Angiotensin II Systemic arterioles Adrenal cortex Posterior pituitary Hypothalamic neurons Vasoconstriction Aldosterone secretion ADH secretion Thirst stimulation Kidneys Sodium reabsorption Water reabsorption in late distal tubules in late distal tubules and collecting ducts and collecting ducts Extracellular fluid osmolarity Plasma volume MAP Kidney Reabsorption and Secretion Review. Glomerulus/Bowman’s Capsule: Bulk Flow “Plasma Like” Filtration Proximal Tubule: (Mass Reabsorber) Significant unregulated re-absorption Loop of Henle: Establishes medullary osmotic gradient Used later for water reabsorption Distal tubule/Collecting Ducts: Regulated re-absorption. Ex. Water, Na+ Secretion of K+ and H+. Fluid Remaining in Collecting Duct Drains To minor/major calyx (cavities) and on to ureter. Ureter connects kidneys to bladder. Micturition (Urination) Is Mediated By a Spinal Cord Reflex. Brain can override for a time… Ureters from both kidneys drain urine into bladder for storage. Urine pressure on bladder walls causes stretch. Reflex initiated in spinal cord: Activation of Parasympathetic- causes contraction of detrusor muscle, Inhibition of Sympathetic- relaxes internal sphincter- urine escapes. The Kidneys Help Regulate Blood pH. (H+) Blood/Body pH Regulation Occurs via Three Mechanisms. Buffering of hydrogen ions Respiratory compensation Renal compensation Normal pH = 7.38 – 7.42 < 7.35 = Acidosis >7.45 = Alkalosis Changes can affect protein conformation/function- Acidosis = Depression of Nervous system- confusion, coma, death Alkalosis = Hyper-excitability of neurons Buffering is The Quickest Defense Against Changes in pH. Acts within seconds. Only “sequesters” H+ can’t really get rid of it. Bicarbonate is an important Extracellular Buffer. HCO3- + H+  H2CO3 (carbonic acid) H2CO3 CO2 + H2O Intracellular Buffers: Proteins: Protein- + H+  HProtein Phosphates: HPO42- + H+  H2PO4- Respiratory System Helps Regulate Blood pH. Second line of defense- acts within minutes. As H+ levels increase (acidosis) Increase ventilation Get rid of CO2 Shift equation to the “left” Carbonic Anhydrase CO2 + H2O  H2CO3  HCO3- + H+ Lowers H+ levels  Renal Compensation For Blood pH Changes. Third line of defense- takes hours to days. Both Proximal and Distal Tubules secrete H+. Example: Distal Tubule: H+ Pump (ATP) Distal tubules secrete H+ and reabsorb HCO3- (which acts as a buffer…) Lung Problems Can Cause: Respiratory Acidosis Hypoventilation Build up of CO2 Respiratory Alkalosis Hyperventilation Too little CO2  Metabolic Acidosis Decrease in pH through something other than carbon dioxide issues Renal dysfunction High protein diet (amino acids…) High fat diet (Keto-acids from fat breakdown) Heavy exercise (lactic acid) Severe diarrhea (loss of bicarbonate) Metabolic Alkalosis Increase pH through something other than carbon dioxide issues Renal dysfunction Excessive vomiting (loss of hydrogen ions) Consumption of alkaline products (baking soda)  Acid-Base Disturbance Compensation Via Lungs or Kidneys. Arterial pH pH < 7.35 OR pH > 7.45 Acidosis Alkalosis [HCO3–] < 24 mM OR PCO > 40 mm Hg [HCO3–] > 24 mM OR PCO < 40 mm Hg 2 2 Metabolic acidosis Respiratory acidosis Metabolic alkalosis Respiratory alkalosis Respiratory Renal Respiratory Renal compensation compensation compensation compensation PCO < 40 mm Hg [HCO3–] > 24 mM PCO > 40 mm Hg [HCO3–] < 24 mM 2 2  Diagnosing pH Problems- Caused by Either Respiratory or Metabolic Problems: When you don’t know what to do…. look to CO2! Acidosis: (high H+, low pH) If CO2 is high = Respiratory acidosis If CO2 is low = Metabolic acidosis (respiratory compensating) Alkalosis: (low H+, high pH) If CO2 is low = Respiratory alkalosis If CO2 is high = Metabolic alkalosis (respiratory compensating)