Renal Physiology The kidneys 5 functions 1)Regulation of body fluid volume 2)Regulation of Osmolarity & Ion Balance 3)Regulation of pH 4)Excretion of Wastes 5)Synthesis of Hormones

Kidney Anatomy Blood enter/leaves via Renal artery/vein Urine leaves via Ureter

Nephron

Nephron: 4 ways substances move Blood Filtrate Urine

Filtration Bowman’s Capsule Podocyte Glomerulus Glomerular capillary Proximal tubule Efferent Arteriole Afferent Arteriole ~ 20% PLASMA entering Glomerulus enter NEPHRON by BULK FLOW!

What is filtered? Filtrate in Nephron contains Plasma (ions, waters, small molecules) It SHOULD NOT contain large proteins or blood cells (they can’t fit through Pores/Slits) VIDEO

How much is filtered? Normal: 125 ml/Min = 180 L/day = Glomerular Filtration Rate Your plasma is filtered 60 times per day! Blood flow to kidney MUST be HIGH

Control of Filtration Rate Local mechanisms alter the diameter of the afferent arteriole Bowman’s Capsule Podocyte Glomerulus Glomerular capillary Proximal tubule Efferent Arteriole Afferent Arteriole Macula Densa (Ascending LOH) Macula Densa releases local control chemicals (ATP, ADP, NO)

Control of Filtration Rate Sympathetic ANS: vasoconstriction of afferent & efferent arterioles REDUCED FLOW, decreased Filt. Rate Hormones: Angiotensin II > vasoconstriction > decreased Filt. Rate Prostaglandins > vasodilation > increased Filt. Rate Angiotensin II & Prostoglandins also affect the size of the filtration slits!

Reabsorption: What is reabsorbed? 99% of molecules entering renal tubule are reabsorbed into peritubular capillaries! Na+, K+, Ca2+, Glucose, Water, Cl-, Urea, small proteins

Renal Tubule ISF Na+ reabsorbed by Active Transport! Na+ Anions Water Ca2+ K+ Urea Na+ Electrical Gradient Anions (-) reabsorbed Reabsorption Active Transport of Na+ DRIVES REABSORPTION!!!!!!! Everything else is DIFFUSION (electrical or concentration gradient) Osmotic gradient (high ISF) Water reabsorbed High Renal Tubule Conc. Other molecule diffuse down conc. gradients hypertonic

Glucose Reabsorption 100% of Glucose is normal blood glucose levels Diabetes mellitus > elevated blood glucose >> glucosuria

Secretion FROM Peritubular Capillary TO Renal Tubule Organic molecules (too big for Filtration), K+, H+ are key molecules SECRETED

Penicillin (Antibiotic) 4 hours: plasma conc. of penicillin = 0 100% of Penicillin is EXCRETED by 4 hours Penicillin is filtered & secreted

1.5 L/Day 180 L/Day L/Day + 0 = Water Glucose 200 mg/min mg /min + 0 =0 mg/min Excretion

Fluid and Electrolyte Balance Why does your body maintain fluids and electrolytes in a balanced state? Na + & Water determine blood volume and pressure K + is essential for resting membrane potential in excitable cells H + and HCO 3 - are key in maintaining pH Ca 2+ is a key signaling ion Integrative, multisystem task; kidney, cardiovascular, respiratory, neural

Water Homeostasis Diarrhea can INCREASE Living in DRY Places can INCREASE 8 – 8oz waters 9 oz from food You body maintains water homeostasis, PRIMARILY, by altering urine volume!

Water Reabsorption Important: Water reabsorption in the LOH is ALWAYS on (unless drugs are present) Your body ONLY alters water reabsorption in the distal tubule & collecting duct!

Variable Water Reabsorption Antidiuretic Hormone (ADH) = Vasopressin Vasopressin (ADH) & Aquaporins Antidiuresis = little concentrated urineDiuresis = lotsa dilute urine

What drives ADH release? 1)Blood Osmolarity High OSM > Increase ADH Low OSM > Decrease ADH 2) Blood Volume 3) Blood Pressure Low BP> Increase ADH High BP> Decrease ADH

Sodium Homeostasis Na+ balance is intimately tied to blood pressure and volume homeostasis! 25% of Adult Americans are Hypertensive Hypertension = Leading Cause of Cardiovascular Death! Excess SALT Intake is Major contributing Factor Americans consume : grams per day NAS recommended: 2 grams per day

Effect of ingested Sodium on Kidney Function ASSUME: Each day you consume 2 grams of salt This could increase you blood osmolarity to 307 mosm/L Cardiovascular Atrial natriuretic peptide (ANP) Aldosterone Pathway Aldosterone Pathway Renal = Renin-Angiotensin-Aldosterone Pathway Renin-Angiotensin-Aldosterone Pathway

Sodium Reabsoption is variable ONLY in the distal tubule and collecting duct Aldosterone: Adrenal hormone that regulates Na+ reabsorption Aldosterone : more Na-K ATPase pumps more K+ and Na+ channels

Aldosterone Release controlled by Osmolarity Adrenal Cortex Reduce Aldosterone Synthesis Sodium Excretion Aldosterone Release is also controlled by Blood pressure Renin-Angiotensin-Aldosterone Pathway

Angiotensinogen in the plasma ANG I in plasma Renin Liver constantly produces produce contains Blood vessel endothelium ACE (enzyme) ANG II in plasma Kidney Adrenal Cortex Aldosterone Synthesis Sodium Reabsorption Hypothalamus ADH Synthesis Thirst Water Reabsorption Vasoconstrict Sympathetic Activation Heart Vasculature Low Blood Pressure Increase Blood Volume Increase Blood Pressure enhances

Aldosterone Release controlled by Osmolarity Adrenal Cortex Reduce Aldosterone Synthesis Sodium Excretion Aldosterone Release is also controlled by Blood pressure Renin-Angiotensin-Aldosterone Pathway

Angiotensinogen in the plasma ANG I in plasma Renin Liver constantly produces produce contains Blood vessel endothelium ACE (enzyme) ANG II in plasma Kidney Adrenal Cortex Reduce Aldosterone Synthesis Sodium Excretion Hypothalamus Reduce ADH Synthesis Thirst Water Excretion Vasodilation Sympathetic Activation Heart Vasculature High Blood Pressure Reduce Blood Volume Lower Blood Pressure enhances ACE inhibitor drug for HYPERTENSION

Adrenal Cortex Reduce Aldosterone Synthesis Sodium Excretion Reduce ANG II Cardiovascular

Atrial Natiuretic Peptide (ANP) BP Blood Volume Atrial Stretch ANP secretion Decreased ADH Decreased Renin Decreased Aldosterone Decreased Sympathetic Lower Blood Pressure Lower Blood Volume Increase Water Excretion Increase GFR Increase Na+ Excretion

Adrenal Cortex Reduce Aldosterone Synthesis Sodium Excretion Reduce ANG II Increase ANP Decrease Symp. General Pathways for Sodium, Blood Volume, and Blood Pressure Homeostasis

More H+ ions Few H+ ions pH Review

Acid-Base Homeostasis: pH pH is affected by the concentration of H+ Your body maintains pH at , precisely! Low pH = acidosis (reduced CNS function) High pH = alkalosis…hyperexcitable membranes (diaphragm arrest!)

Where do acids (H+ ions) come from? H+ is always being produced ….so… H+ always needs to be excreted

3 mechanisms of pH homeostasis 1)Buffering systems 2)Lungs 3)Kidneys – 25% 75% Loss of any mechanism can lead to ACIDOSIS > lowered blood pH

CO 2 + H 2 O ↔ H 2 CO 3 ↔ H + + HCO 3 - Law of Mass Action CO 2 + H 2 O H 2 CO 3 H + + HCO 3 - H+ combines with HCO3- to BUFFER the effect of increase H+ CO 2 + H 2 O ↔ H 2 CO 3 ↔ H + + HCO 3 - More CO2 & H2O are produced by buffering actionHCO3- is used up The buffer of H + is HCO 3 - HCO 3 - is 600,000 x more concentrated than H + in blood

Respiratory Regulation of pH CO 2 + H 2 O ← H 2 CO 3 ← H + + HCO 3 - Brainstem chemoreceptors Increased Ventilation Rate and Volume CO 2 + H 2 O → H 2 CO 3 → H + + HCO 3 - Carotid & Aortic chemoreceptors

Renal Regulation of pH- 25% Always ON 1)Reabsorbtion of HCO3- ; indirect excretion of H+ Always ON PROXIMAL Renal Tubule Nephron Cell Renal ISF Peritubular Capillaries HCO 3 - H 2 CO 3 H 2 O + CO 2 Filtered HCO3- cannot be directly reabsorbed C.A. H 2 O + CO 2 H 2 CO 3 H+H+ HCO 3 - ATPase HCO 3 - H+H+ NH 4 + Ammonium Ion H 2 PO 4 - Phosporic Acid NH 3 Hydrogen Phosphate Ion HPO 4 2- Most Filtered H+ is not directly excreted Amino Acids HCO 3 - REABSORBTION

Skeletal System: Functions 1)Support 2)Movement 3)Calcium Homeostasis!

Parathyroid Gland Ca2+ receptors are linked to G-protiens that control the release of PTH (parathyroid hormone)!

Calcium Homeostasis Ca2+ Receptors in Parathyroid gland monitor blood Ca2+ levels 1)If Ca2+ Low – PTH released Bone breaks down releasing Ca2+ Kidney reabsorbs Ca2+ Intestines uptake more Ca2+ 2)If Ca2+ High – PTH syn. inhibited Bone building, incorporating Ca2+ Kidney does not reabsorb Ca2+ Intestines do not uptake Ca2+ Bone accounts for 99% of the calcium reserves in your body!

Osteoporosis Osteoporosis is linked to long-term low dietary intake of Ca2+ Bone Loss > Bone Building… so that Ca2+ levels are maintained Ca2+ is a key ion everywhere!!!! Women are more susceptible than men….lower bone mass & menopausal estrogen decrease