Urinary System - A&P II Rodenbeck
Lithotripsy
"simple" stones too large to pass through ultrasound shock waves smaller pieces pass out of body in urine
Kidney Physiology: Urine Formation
*Glomerular filtration* - produces cell- and protein-free filtrate (into filtrate; size) *Tubular reabsorption* Selectively returns 99% of substances from filtrate to blood in renal tubules and collecting ducts (into blood, highly selective) *Tubular secretion* Selectively moves substances from blood to filtrate in renal tubules and collecting ducts (backwards reabsorption, highly selective, into filtrate)
Nephron Capillary Beds
*Glomerulus* *Afferent arteriole -> glomerulus -> efferent arteriole (fed and drained by arteriole)* - Specialized for filtration (fenestrated capillaries) - Blood pressure is high because 1. Afferent arterioles are larger in diameter than efferent arterioles 2. Arterioles are high resistance vessels - high BP makes it even better for filtration
Cells of the Juxtaglomerular Apparatus (JGA)
*Granular cells* (juxtaglomerular, or JG cells) Enlarged, smooth muscle cells of arteriole Secretory granules contain renin Act as mechanoreceptors that sense blood pressure (sense stretch) - in afferent arteriole
Allocation of water losses
*If water is lost, but electrolytes retained*: - ECF osmotic concentration rises - becomes hypertonic to ICF - Fluid shifts from ICF (cells) to ECF (blood, interstitial) - May result in dehydration *If water is gained, but electrolytes are not*: - ECF volume increases - ECF becomes hypotonic to ICF - fluid shifts from ECF to ICF (into cells) - may result in overhydration - *lose water from body -> lose water from ECF -> incr. osmotic pressure of ECF -> pull water from cells into ECF -> cells shrink*
Cells of the Juxtaglomerular Apparatus (JGA) (part 2)
*Macula densa* Tall, closely packed cells of the DCT Act as chemoreceptors that sense NaCl content of filtrate - columnar cells *Extraglomerular mesangial cells* Interconnected with gap junctions (cell to cell communication) Pass signals between macula densa and granular cells
Nephron capillary beds part 2
*Peritubular capillaries* - Low-pressure, porous capillaries adapted for absorption - Arise from efferent arterioles - Cling to adjacent renal tubules in cortex - Empty into venules - Readily absorb solutes and water from tubule cells as they reclaim these from filtrate. - Renal tubules closely packed together so capillaries reabsorb from several nephrons - capillaries that surround tubes
*Stop for Quiz* Urine output if Na+ channels in tubule cells inhibited?
*Stop for Quiz* Volume would increase (b/c sodium doesn't go out, stays in, brings water in, stays in filtrate, water increase in filtrate)
Nephron Capillary Beds part 3
*Vasa recta* - Bundles of long "straight vessels" parallel to long loops of Henle - Arise from efferent arterioles of juxtamedullary nephrons - Thin walled - Function in formation of concentrated urine (work w/ nephron loop) - similar to peritubular capillary
path of blood flow through renal blood vessels
*know* - two capillary beds 1. no gas exchange in glomerulus capillary bed 2. gas exchange in peritubular capillary bed *A Really Sweet Ice And Cream Are Good Every Vacation Particularly Combined All Inside Real Igloos*
Formation of Dilute or concentrated urine
*see print out*
Kidney location
- Retroperitoneal - Superior Lumbar region (T12-L3) - Right kidney crowded by liver and lies slightly lower than left
Acid-base balance in blood (Metabolic)
- *Metabolic acidosis* results from excess of acids E.g. excess ketone bodies in diabetes or loss of HCO3- (for buffering) in diarrhea - *Metabolic alkalosis* caused by too much HCO3- or too little acid (e.g. from vomiting out stomach acid)
Supportive tissue
- *Renal Fascia*: Outer layer of dense, fibrous connective tissue - anchors kidney and adrenal gland to surrounding structures. - *Perirenal fat capsule*: Fatty mass that surrounds kidney and cushions it against blows. - *Fibrous capsule*: Transparent capsule that prevents infections in surrounding regions from spreading to kidney
Acid-base balance in blood (Respiratory)
- *respiratory acidosis* caused by hypoventilation causes rise in blood cO2 (hypercapnia) and thus carbonic acid - *respiratory alkalosis* caused by hyperventilation results in too little CO2 (hypocapnia)
Role of aldosterone in Na+/K+ balance
- 90% filtered Na+ and K+ reabsorbed before DCT - Remaining is variably reabsorbed in DCT and cortical CD according to bodily needs 1. Regulated by aldosterone (controls K+ secretion and Na+ reabsorption) 2. In the absence of aldosterone, 80% of remaining Na+ is reabsorbed in DCT and cortical CD 3. When aldosterone is high all remaining Na+ is reabsorbed
Chemical composition of urine
- 95% water and 5% solutes - Nitrogenous wastes: urea, uric acid, and creatinine - Other normal solutes - Na+, K+, PO43-, and SO42-, - Ca2+, Mg2+ and HCO3- - Abnormally high concentrations of any constituent may indicate pathology
Signs of Overhydration
- Abnormally low Na+ concentrations (hyponatremia) - Effects on CNS function (water intoxication-drunk behavior) - Apathy, confusion, nausea, fatigue, hallucinations, convulsions, coma and death possible
Vascular resistance in microcirculation
- Afferent and efferent arterioles offer high resistance to blood flow - Blood pressure declines from 95mm Hg in renal arteries to 8 mm Hg in renal veins - *Resistance in afferent arterioles (constrict):* - Protects glomeruli from fluctuations in systemic blood pressure - *Resistance in efferent arterioles (constrict):* - Reinforces high glomerular pressure - Reduces hydrostatic pressure in peritubular capillaries - renal artery pressure high b/c comes off aorta - glomeruli are capillaries and can't handle high pressure/fluctuation
Over hydration
- Also called water excess - Caused by ingestion, inability to eliminate excess in urine, endocrine disorders - Occurs when excess water shifts into ICF (incr. ECF volume -> decr. concentration -> water moves into cells) : 1. distorting cells 2. changing solute concentrations around enzymes 3. disrupting normal cell functions
Electrolytes: cations and anions
- Are ions released through dissociation of inorganic compounds that can conduct electrical current in solution (can hold more water since they dissociate) - In ECF: *sodium*, chloride, and bicarbonate - In ICF: *potassium*, magnesium, and phosphate ions negatively charged proteins
Osmotic concentration: vasa recta
- Blood entering the vasa recta (descending) has an osmotic concentration of 300 mOsm/L - Concentration increases as blood descends into medulla - Water diffuses out to interstitial fluid - Solutes present in interstitial fluid diffuse into *descending vasa recta* - These movements occur because concentration (osmolality) is higher in the interstitial fluid than in vasa recta
Osmotic concentration: vasa recta (part 2)
- Blood flowing toward cortex (ascending) - Water flows into ascending vessels because of high osmotic pressure in vasa recta. 1. More water is moved into the ascending portion than is moved out in the descending portion. This removal of water from the medulla is critical to maintain hypertonicity of medullary interstitial fluid. 2. Solute moves out of the vasa recta into interstitial fluid 3. These movements occur because the osmolality is higher in the vasa recta than interstitial fluid *Summary: Water is removed from the kidney to the blood and the solutes are recirculated to maintain concentration gradient.* - reclaim water = blood volume and amount of water in urine - need salty environment in medulla to keep gradient there
Intrinsic Controls of GFR - Myogenic Mechanism
- Can control filtration by controlling blood flow into glomerulus (hydrostatic pressure) - Smooth muscle contracts when stretched 1. *incr BP -> muscle stretch -> constriction of afferent arterioles -> restricts blood flow into glomerulus* - Protects glomeruli from damage due to high BP 2. *decr BP -> dilation of afferent arterioles and constriction of efferent (decreases pressure in peritubular capillaries or vasa recta and increases time for reabsorption)* - Both help maintain normal GFR despite normal fluctuations in blood pressure
Abnormal Na+ Concentrations in ECF
- Caused by severe problems with fluid balance - normal = 142 mEq/L *Hyponatremia* (low blood Na+): - body water concentration rises (overhydration) - ECF Na+ concentration < 130 mEq/L *Hypernatremia* (high blood Na+): - body water concentration declines (dehydration) - ECF Na+ concentration > 150 mEq/L - *if sodium decreases in ECF, there is a higher water to solute concentration in ECF; to fix this water moves into the ICF in the cells; and vice versa*
Diuretics
- Chemicals that *enhance the urinary output* include: - Any substance not reabsorbed (any solute contributing to osmotic pressure and holding water) - Substances that exceed the ability of the renal tubules to reabsorb it - Substances that inhibit Na+ reabsorption - Block Na+-associated transporters in ascending limb (tubular reabsorption from filtrate to tubule cells) so Na+ (and water that follows it) remains in filtrate
Regulation of glomerular filtration part 1 (goals of each)
- Constant GFR allows kidneys to make filtrate and maintain extracellular homeostasis 1. *Goal of intrinsic controls - maintain GFR in kidney* - GFR affects systemic blood pressure - incr. GFR = incr. urine output = decr. blood pressure, and vice versa 2. *Goal of extrinsic controls - maintain systemic blood pressure* - originally an increase in GFR increases NFP which increases BP which needs to be lowered - *GFR and NFP are directly proportional*
Regulation of glomerular filtration part 3 (involving GFR)
- Controlled via glomerular hydrostatic pressure - *If GHP rises -> NFP rises -> GFR rises* - If GHP falls only 18%, then GFR = 0 - If the GFR is too high: Needed substances cannot be reabsorbed quickly enough and are lost in the urine - If the GFR is too low: Everything is reabsorbed, including wastes that are normally disposed of
Kidney external anatomy
- Convex lateral surface, concave medial surface - Renal hilum leads to renal sinus - Cleft in medial concave side: *Renal Hilum* - Ureters, renal blood vessels, lymphatic vessels, and nerves enter and exit at the hilum
Countercurrent Multiplication
- Countercurrent - tubular fluid in the ascending and descending limbs travel in opposite direction - Multiplication - multiplies the effect on H20 reabsorption in the descending limb, filtrate concentration in descending limb, and NaCl transport in the ascending limb. Positive feedback relationship - *creates medullary gradient*
Renal tubule parts (3)
- Distal convoluted tubule (DCT) - Cuboidal cells with very few microvilli - Function more in secretion than reabsorption Confined to cortex
Benefits of Countercurrent Multiplication (AKA: Why Do We Care?)
- Efficiently reabsorbs solutes and water before tubular fluid reaches DCT and collecting duct - Establishes concentration gradient that permits passive reabsorption of water from the collecting ducts as they pass thru the medulla.
Urinary buffers
- Excretes more H+ by buffering H+s with anion in filtrate before excretion - Nephron cannot produce urine with pH < 4.5 - Buffering reactions (bind with weak acid): HPO4-2 + H+ H2PO4- NH3 + H+ NH4+ (ammonium ion) - Phosphate enters tubule during filtration and - Ammonia made in tubule by deaminating amino acids - For each H+ excreted, we reabsorb an HCO3-
Intrinsic Controls of GFR - Tubuloglomerular Feedback Mechanism
- Flow-dependent mechanism directed by macula densa cells; respond to filtrate NaCl concentration (GFR) 1. *If GFR incr -> filtrate flow rate incr -> decr reabsorption time -> high filtrate NaCl levels at macula densa (sense incr. in NaCl signal thru EMC to granular cells) -> constriction of afferent arteriole by ATP -> decr NFP & GFR -> more time for NaCl reabsorption* 2. Opposite for decr GFR (inhibits ATP release, so dilation instead of constriction)
Regulation of sodium balance
- If ECF (blood or interstitial fluid) volume is *low* 1. blood volume and blood pressure decline 2. renin-angiotensin system is activated 3. ADH and aldosterone released 4. water and Na+ (both enhances water reabsorption) losses are reduced 5. ECF volume increases - *inadequate NaCl intake is always accompanied by fall in blood volume* - negative feedback mechanism
Extrinsic Regulation of Low GFR
- If GFR is reduced, the fluid moves slowly - This means it is in the ascending limb of the loop of Henle longer so more Na+ is reabsorbed - The concentration of Na+ and Cl- ions reaching the macula densa and DCT becomes abnormally low - Stimulation of these JG cells by the macula densa causes release of renin, angiotensin. - Angiotensin II increases systemic blood volume and blood pressure - Restoration of normal GFR
Extrinsic Controls of GFR - Sympathetic Nervous System (part 2)
- If extracellular fluid (blood/interstitial fluid) volume extremely low (blood pressure low) - Norepinephrine released by sympathetic nervous system; epinephrine released by adrenal medulla -> 1. Systemic vasoconstriction -> increased blood pressure 2. Constriction of afferent arterioles -> decr GFR -> increased blood volume (*through renin release and reabsorption*) and pressure = incr. BV incr. BP
regulation of glomerular filtration part 2 (mechanisms of each)
- Intrinsic controls (renal autoregulation) - Act locally within kidney to maintain GFR - Extrinsic controls (goal is to fix BP not kidney) - Nervous and endocrine mechanisms that maintain blood pressure; can negatively affect kidney function - Take precedence over intrinsic controls if systemic BP < 80 or > 180 mm Hg
Pressures that affect filtration continued...
- Inward forces inhibiting filtrate formation 1. Hydrostatic pressure in capsular space (HPcs) Pressure of filtrate in capsule - 15 mm Hg 2. Colloid osmotic pressure in capillaries (OPgc) "Pull" of proteins in blood - 30 mm Hg - *Sum of forces -> Net filtration pressure (NFP)* Ex. 55 mm Hg forcing out; 45 mm Hg opposing = net outward force of 10 mm Hg *(GHP)-(HPcs+OPgc) = NFP*
intracellular fluid vs extracellular fluid
- Is identical - Osmosis eliminates minor differences in concentration: - Because cell membranes are permeable to water 1. intracellular fluid 2. extracellular fluid (interstitial fluid and plasma)
renal acid-base regulation
- Kidneys help regulate blood pH by excreting H+ and/or reabsorbing HCO3- - Most H+ secretion occurs across walls of PCT in exchange for Na+ (Na+/H+ transporter) - Normal urine is slightly acidic (pH = 5-7) because kidneys reabsorb almost all HCO3- and excrete H+
Electrolyte balance
- Kidneys regulate levels of Na+, K+, H+, HCO3-, Cl-, and PO4-3 by *matching excretion to ingestion* - Control of plasma *Na+* is important in regulation of blood volume and pressure (*water follows salt*) - Control of plasma *K+* is important in proper function of cardiac and skeletal muscles (resting membrane potential)
Two types of metabolic acidosis
- Lactic acidosis: produced by anaerobic cellular respiration after muscular activity. - Ketoacidosis: produced by excess ketone bodies in starvation or diabetes. Beta oxidation of fat molecules.
Filtration Membrane continued
- Macromolecules "stuck" in filtration membrane engulfed by *glomerular mesangial cells* - Allows molecules smaller than 3 nm to pass - Water, glucose, amino acids, nitrogenous wastes - Plasma proteins remain in blood -> maintains blood colloid osmotic pressure (BCOP) -> prevents loss of all water to capsular space - Proteins in filtrate indicate membrane problem
Intrinsic Controls of GFR (what is required for it to work?)
- Maintains nearly constant GFR when MAP in range of 80-180 mm Hg - Autoregulation ceases if out of that range - Two types of renal autoregulation 1. Myogenic mechanism 2. Tubuloglomerular feedback mechanism (JGA)
Urinary buffers (part 2)
- Most important buffer in blood is bicarbonate: H2O + CO2 ⇌ H2CO3 ⇌ H+ + HCO3- (catalyzed carbonic anhydrase (CA)) - Excess H+ is buffered by HCO3- - Kidney's role is to excrete H+ into urine
Tubular reabsorption
- Most of tubular contents reabsorbed to blood Selective process ~ All organic nutrients reabsorbed - Water and ion reabsorption hormonally regulated and adjusted (*ADH, Aldosterone*) - *Includes active and passive reabsorption* - *highly selective process*
Passive Tubular Reabsorption of Water
- Movement of Na+ and other solutes creates osmotic gradient for water - Water reabsorbed by osmosis, aided by water-filled pores called *aquaporins* - Aquaporins always present in *PCT* -> *obligatory water reabsorption* - Aquaporins inserted in *collecting ducts only if ADH present* -> *facultative water reabsorption*
Tubular reabsorption of Na+
- Na+ - most abundant cation in filtrate 1. Transport across basolateral membrane - Primary active transport out of tubule cell by *Na+-K+ pump* -> peritubular capillaries 2. Transport across apical membrane - Na+ passes through apical membrane by *secondary active transport or facilitated diffusion mechanisms*
Reabsorption of nutrients, water, and ions
- Na+ reabsorption by primary active transport provides energy and means for reabsorbing most other substances - Creates electrical gradient -> passive reabsorption of anions - Organic nutrients reabsorbed; cotransported with Na+ - Glucose, amino acids, some ions, vitamins
Na+, K+, and H+ relationship
- Na+ reabsorption in DCT and CD creates electrical gradient for H+ and K+ secretion back into filtrate (only one at a time) - *When extracellular (blood) H+ increases -> low pH in blood, H+ moves into tubule cells causing K+ to diffuse out (into blood) and vice versa* - Hyperkalemia can cause acidosis - In severe acidosis, H+ is secreted at expense of K+
Renal tubule parts (2)
- Nephron loop (Loop of Henle) - Descending and ascending limbs - Proximal descending limb continuous with proximal tubule - Distal descending limb = descending thin limb; simple squamous epithelium - Thick ascending limb - Cuboidal to columnar cells - *only part of nephron that dips down into medulla*
Diuretics (part 2)
- Osmotic diuretics include: - High glucose levels - carries water out with the glucose - Alcohol - inhibits the release of ADH - Caffeine and most diuretic drugs - inhibit sodium ion reabsorption - Lasix and Diuril - inhibit Na+-associated symporters - Can cause loss of K+
Formation of dilute or concentrated urine
- Osmotic gradient used to raise urine concentration > 300 mOsm to conserve water 1. Overhydration -> large volume dilute urine - ADH production decr ; urine ~ 100 mOsm - If aldosterone present, additional ions removed (Na+ is retained in body and leaves filtrate) -> ~ 50 mOsm 2. Dehydration -> small volume concentrated urine - Maximal ADH released; urine ~ 1200 mOsm - Severe dehydration - 99% water reabsorbed - Obligatory water loss - 400 ml/day needed to excrete metabolic wastes produced.
Pressures that affect filtration
- Outward pressures promote filtrate formation - *Hydrostatic pressure in glomerular capillaries (GHP)* = Glomerular blood pressure - Chief force pushing water, solutes out of blood - Quite high - 55 mm Hg (most capillary beds ~ 26 mm Hg) - Because efferent arteriole is high resistance vessel with diameter smaller than afferent arteriole
Glomerular Filtration
- Passive process, no metabolic energy required - Hydrostatic pressure forces fluids and solutes through filtration membrane - No reabsorption into capillaries of glomerulus (filtration only) - bring blood by HBP, force substance out of blood into glomerular capsule (collecting space)
Filtration Membrane
- Porous membrane between blood and interior of glomerular capsule - Water, solutes smaller than plasma proteins pass; normally no cells pass - filter based on size (if small enough) - Three layers 1. *Fenestrated endothelium* of glomerular capillaries 2. *Basement membrane* (fused basal laminae of two other layers) 3. *Foot processes of podocytes* with filtration slits; slit diaphragms repel macromolecules
Net filtration pressure
- Pressure responsible for filtrate formation (10 mm Hg) - *Main controllable factor determining glomerular filtration rate (GFR)* - *how fast it is forming filtrate at the glomerulus*
Renal tubule parts (1)
- Proximal convoluted tubule (PCT) - Cuboidal cells with dense microvilli (brush border surface area); large mitochondria - Functions in reabsorption of water and solutes from filtrate and secretion of substances into it - confined to cortex
collecting ducts
- Receive filtrate from many nephrons - Run through medullary pyramids -> striped appearance - Fuse together to deliver urine through papillary ducts and papillae into minor calyces
Kidney function overview
- Regulate total volume of water in the body (ADH) and total concentration of solutes in that water (aldosterone) - Regulate concentrations of various ions in the extracellular fluids - Ensure long-term acid-base balance (mainly lungs) - Excrete metabolic wastes and foreign substances - Produce erythropoietin and renin - Convert vitamin D to its active form - Carry out gluconeogenesis during prolonged fasting
Kidney function overview continued
- Regulate volume and chemical makeup of the blood. Maintain the proper balance between water and salts, and acids and bases. - Filter 180-200 liters of blood daily, 7.5L/hr, 45 gallons. Total blood volume is filtered every 40 mins., total plasma volume every 60 mins. - Filtration consumes 20-25% oxygen used by body at rest, allowing toxins, metabolic wastes, and excess ions to leave the body in urine. - 1500 ml urine/day, < 1% filtrate, Osmotic conc. 800-1000mOsm/L - If most of filtered water isn't returned to the vascular system, you would urinate to death in minutes!
Nephrons information
- Renal corpuscle - Glomerulus + its glomerular capsule - Fenestrated glomerular endothelium - Allows filtrate to pass from plasma into the glomerular capsule
Blood and nerve supply
- Rich blood supply -> kidneys cleanse blood and adjust its composition - Renal arteries deliver ~ ¼ (1200 ml/min) of cardiac output to kidneys - Arterial flow into and venous flow out of kidneys follow similar paths - Nerve supply via sympathetic fibers from renal plexus
Urinary Bladder
- Smooth, collapsible, muscular sac that stores urine - It lies retroperitoneally on the pelvic floor posterior to the pubic symphysis Males - prostate gland surrounds the neck inferiorly Females - anterior to the vagina and uterus - *Trigone* - triangular area outlined by the openings for the ureters and the urethra - Clinically important because infections tend to persist in this region
Passive tubular reabsorption of solutes
- Solute concentration in filtrate increases as water reabsorbed -> incr solute concentration -> concentration gradients for solutes - Fat-soluble substances, some ions and urea, follow water into peritubular capillaries *down* concentration gradients -> Lipid-soluble drugs, environmental pollutants difficult to excrete because they easily pass through the lipid bilayer membrane down concentration gradients. (keep being reabsorbed) *reabsorption* = out of filtrate into blood
nephrons
- Structural and function units of the kidney that form urine - > 1 million nephrons per kidney - Two basic parts: 1. *Renal corpuscle* - Glomerulus Contains fenestrated endothelium - Glomerular capsule 2. *Renal tubule* *know how to label this picture*
Urethra info (female vs. male)
- The female urethra is tightly bound to the anterior vaginal wall Its external opening lies anterior to the vaginal opening and posterior to the clitoris - The male urethra has three named regions 1. Prostatic urethra - runs within the prostate gland 2. Membranous urethra - runs through the urogenital diaphragm 3. Spongy (penile) urethra - passes through the penis and opens via the external urethral orifice
Ureters layers
- Three layers of wall of ureter - Lining of transitional epithelium - Smooth muscle muscularis - Contracts in response to stretch - Ureters use peristalsis for flow of urine - Outer adventitia of fibrous connective tissue
Transport maximum
- Transport maximum (Tm) for *every reabsorbed substance; reflects number of carriers* in renal tubules available for facilitated diffusion or cotransport mechanisms. - When carriers saturated (all carriers are busy), excess excreted in urine. E.g., hyperglycemia -> high blood glucose levels exceed Tm and renal threshold (plasma concentration) of 180mg/dl -> glucose in urine (gycosuria) - excess glucose in urine holds water and more urine is excreted w/ glucose
collecting ducts cell types
- Two important cell types are found here 1. *Intercalated cells* - Cuboidal cells with microvilli - Function in maintaining the acid-base balance of the body 2. *Principal cells* - Cuboidal cells without microvilli - Help maintain the body's water and salt balance - target cells of hormones
Diuresis
- Typically indicates production of large volumes of urine - *Diabetes insipidus* - when a large volume of dilute urine is excreted due to inadequate ADH secretion - *Diabetes mellitus* - due to loss of glucose in the urine which is a major solute pulling water with it. - High glucose in plasma due to inadequate or failing insulin.
Urea recycling and the medullary osmotic gradient
- Urea helps form medullary gradient - Enters filtrate in ascending thin limb of nephron loop by facilitated diffusion - Cortical collecting duct reabsorbs water; leaves urea - In deep medullary region now highly concentrated urea -> interstitial fluid of medulla -> back to ascending thin limb -> high osmolality in medulla
Micturition
- Urination or voiding - Trigger is bladder walls stretching Three simultaneous events 1. *Contraction of detrusor muscle by ANS* 2. *Opening of internal urethral sphincter by ANS* 3. *Opening of external urethral sphincter by somatic nervous system*
Problems with electrolyte balance
- Usually result from sodium ion imbalances - Potassium imbalances are less common, but more dangerous (*resting membrane potentials are directly related to K+ conc.*) 1. *Hyperkalemia* - increase in K+ blood levels 2. *Hypokalemia* - decrease in K+ blood levels - Either of these can cause heart arrhythmias and abnormal skeletal muscle contractions.
Glomerular filtration rate
- Volume of filtrate formed per minute by both kidneys (normal = 120-125 ml/min) - GFR is directly proportional to 1. *NFP* - primary pressure is hydrostatic pressure in the glomerulus (incr. NFP = incr. GFR) 2. *Total surface area available for filtration* - glomerular mesangial cells control by contracting (contract = decr. SA = decr. GFR) 3. *Filtration membrane permeability* - much more permeable than other capillaries (incr. perm = incr. GFR)
renal tubule
- extends beyond capsule continuous with capsule Three parts 1. Proximal convoluted tubule Proximal closest to renal corpuscle 2. Nephron loop - Loop of Henle 2. Distal convoluted tubule Distal farthest away from renal corpuscle
Reabsorption of HCO3- in PCT
- indirect because apical membranes of PCT cells are impermeable to HCO3- - When filtrate is acidic, HCO3- combines with H+ to form H2CO3, which becomes CO2 + H2O (catalyzed by CA on apical membrane of PCT cells) - CO2 and water diffuse into the PCT cell and forms H2CO3 (catalyzed by CA) - H2CO3 splits into HCO3- and H+; HCO3- diffuses into blood
Regulation of water intake: thirst mechanism
- osmoreceptors detect plasma membrane stretch (cells fill with water and stretch) - decr. ECF volume -> decr. saliva (to retain water) - decr. plasma volume -> decr. BP -> inhibit baroreceptors
Acid-base balance (what three things is it regulated by?)
- pH affects all functional proteins and biochemical reactions - normal pH in body (arterial blood = pH 7.4) - *alkalosis*: arterial pH > 7.45 (too basic) - *acidosis*: arterial pH < 7.35 - most H+ produced as by-product of metabolism - regulated by 1. chemical buffer system (rapid) 2. brain stem respiratory centers (within 1-3 minutes of imbalance) 3. renal mechanisms (within hours or days of imbalance)
K+ secretion
- secretion by DCT and CD is only way K+ ends up in urine - Is directed by aldosterone and occurs in DCT and cortical CD 1. High K+ or low Na+ will increase aldosterone and K+ secretion 2. Most important factor for regulating aldosterone is K+ concentration in the ECF - incr. K+ in ECF -> release aldosterone and secrete K+ into filtrate where it is excreted - K+ is filtered by the glomerulus, reabsorbed out of filtrate at the PCT, secreted by the DCT and CD into filtrate, then excreted
Medullary Osmotic Gradient
1) create gradient 2) preserve gradient 3) use gradient see print out
Classes of Nephrons
1. *Cortical nephrons*—85% of nephrons; almost entirely in cortex 2. *Juxtamedullary nephrons* - Long nephron loops deeply invade medulla - Ascending limbs have thick and thin segments - Important in production of concentrated urine - proximal and distal convoluted tubes and glomerulus in cortex
Sodium plays a central role in fluid and electrolyte balance
1. *most abundant* cation in ECF - sodium salts in ECF contribute *280 mOsm* of total 300 mOsm ECF solute concentration 2. only cation exerting *significant* osmotic pressure - controls ECF volume and water distribution between ECF and ICF because water follows salt - changes in Na+ levels affect plasma volume, BP, and ECF and ICF volumes
Effects of Angiotensin II
1. Constricts arteriolar smooth muscle, causing MAP to rise 2. Stimulates the reabsorption of Na+ - Acts directly on the renal tubules and triggers adrenal cortex to release aldosterone (target at principal cells to reabsorb Na+) 3. Stimulates the hypothalamus to release ADH and activates the thirst center 4. *Constricts efferent arterioles, decreasing peritubular capillary hydrostatic pressure and increasing fluid reabsorption*
Glomerular Capsule
1. Parietal layer Simple squamous epithelium Outer layer of the glomerular capsule Contributes to capsule structure but no filtrate-forming role 2. Visceral layer Branching epithelial *podocytes* Extensions terminate in foot processes that cling to basement membrane of glomerulus *Filtration slits* between foot processes allow filtrate to pass into *capsular space*
1. How do we regulate blood pH? 2. Most reabsorption occurs where?
1. Secretion and reabsorption 2. PCT
1. anytime you have movement of just one component across a membrane how are volume and concentration related? 2. increase in solute concentration in ECF causes what? 3. marathon runner is overheated, drinks lots of plain water, end of race is very disoriented...why?
1. inversely proportional 2. water moves out of the cells 2. runner is suffering from hypotonic hydration and her cells fluids are overdiluted (needs electrolytes, ECF is too diluted and losing water to cells)
1. once it filters into globular capsule what is it? 2. what is the blood filtering structure of kidney?
1. no longer blood but is filtrate 2. glomerulus
Membrane permeability to both solutes and water
1. solutes and water molecules move down their concentration gradients in opposite directions. Fluid volume remains the same in both compartments 2. solute molecules are prevented from moving but water moves by osmosis. Volume increases in the compartment with higher osmolarity
Sending so much water out into interstitial fluid, why not dilute?
???
Reabsorptive Capabilities of Renal Tubules and Collecting Ducts Part 5 (Aldosterone)
Aldosterone Targets collecting ducts (principal cells) and distal DCT - Produces apical Na+ and K+ channels, and Na+-K+ Pumps for Na+ reabsorption through active transport and water follows - little Na+ leaves body; in aldosterone absence -> we would lose 2% of filtered Na+ daily which is incompatible with life (need to retain sodium) - Functions - Reabsorb Na+, increase blood pressure, decrease K+ levels (Na+ from filtrate into blood)
Reabsorptive Capabilities of Renal Tubules and Collecting Ducts Part 4 (ADH)
Antidiuretic hormone (ADH) Released by posterior pituitary gland made in hypothalamus Causes principal cells of collecting ducts to insert aquaporins in apical membranes -> water reabsorption As ADH levels increase -> increased water reabsorption - apical membrane faces filtrate (water reabsorb out of filtrate into blood)
Countercurrent Multiplier: Nephron Loop (part 2)
Ascending limb - Impermeable to H2O - Selectively permeable to solutes - Na+ and Cl- actively reabsorbed in thick segment; some passively reabsorbed in thin segment - Filtrate osmolality decreases to 100 mOsm - hyposmotic (100 mOsm < ISF = 300 mOsm)
Reabsorptive Capabilities of Renal Tubules and Collecting Ducts Part 6 (ANP)
Atrial natriuretic peptide (ANP) Reduces blood Na+ and water which causes decreases blood volume and blood pressure Released by cardiac right atrium cells if blood volume or pressure elevated Remember ANP blocks everything that Renin-Angiotensin does. - blocks aldosterone and reabsorption of Na+
Severe Water Loss
Causes: - excessive perspiration - inadequate water consumption - repeated vomiting - Diarrhea *Body fluids become increasingly concentrated and both ICF and ECF are lower (in volume, first in ECF then in cells/ICF) than before - dehydration*
Ureters
Convey urine from kidneys to bladder Retroperitoneal Enter the base of the bladder through the posterior wall at a steep angle. As bladder pressure increases, distal ends of the ureters close, preventing backflow of urine
Reabsorptive Capabilities of Renal Tubules and Collecting Ducts Part 3 (DCT/CD)
DCT and collecting duct Reabsorption *hormonally regulated* Antidiuretic hormone (ADH) - Water Aldosterone - Na+ (therefore water) Atrial natriuretic peptide (ANP) - Blocks Na+ reabsorption (blocks aldosterone and causes Na+ loss.)
Countercurrent Multiplier: Nephron loop
Descending limb - start at 300 mOsm - Freely permeable to H2O (out) - H2O passes out of filtrate into hyperosmotic medullary interstitial fluid - Filtrate osmolality increases to ~1200 mOsm
Developmental aspects
Frequent micturition in infants due to small bladders and less-concentrated urine Incontinence is normal in infants: control of the voluntary urethral sphincter develops with the nervous system. Potty trained by 24-30 mos. E. coli bacteria account for 80% of all urinary tract infections Streptococcal infections may cause long-term renal damage
Severe water loss (part 2)
Homeostatic responses: - physiologic mechanisms (ADH and renin secretion) - behavioral changes (increasing fluid intake) - Prevent shock from significant fall in plasma volume and blood pressure - Clinical therapies include hypotonic fluids by mouth and IV infusion (increase ECF volume (decr. concentration) and promote fluid shift back to ICF to maintain isosmosis)
Regulation of sodium balance (2)
If ECF/plasma volume is *too large*: = BP and BV are high - venous return increases: 1. --stimulating natriuretic peptides (ANP) 2. --reducing thirst 3. --blocking secretion of ADH and aldosterone - salt and water loss at kidneys increases - ECF volume declines
Fluid balance
Is a daily balance between: 1. amount of water gained 2l amount of water lost to environment - *The Digestive System is the primary source of water gains*: - plus a small amount from metabolic activity of cells - *And Urinary System primary source of water loss*
Developmental aspects continued
Kidney function declines with age, with many elderly becoming incontinent 3% of elderly people have normal kidneys. Nephrons decrease in size and number, and the kidneys shrink By age 80, the GFR is half that of young adults. Bladder in elderly holds half of younger adult, approx. 250ml, causing nocturia and frequency of urination.
Renal Calculi
Kidney stones form in renal pelvis Crystallized calcium, magnesium, or uric acid salts Larger stones block ureter, cause pressure and pain in kidneys May be due to chronic bacterial infection, urine retention, incr. Ca2+ in blood, incr. pH of urine
Urinary System Components
Kidneys Ureters Paired tubes that transport urine from the kidneys to the urinary bladder Urinary Bladder A temporary storage reservoir for urine Urethra A tube that caries urine from the bladder to the body exterior
Answer the following in regards to the Loop of Henle and Vasa Recta? 1. what is the ascending/descending limb permeable to? 2. what is the direction of permeability? 3. is it active or passive 4. what are the changes in osmolality of filtrate and where do they occur?
Loop of Henle: 1&2&3. *descending limb* is permeable to water not salt, moving out of the filtrate, passive (increase filtrate osmolality); no movement in the *bend of loop*; *thin ascending limb* permeable to NaCl not water, moving out of filtrate, passive (increase ISF osmolality); *thick ascending limb* permeable to NaCl not water, moving out of filtrate, actively pumped (increase ISF osmolality) 4. starts isosmotic 300 mOsm in the glomerulus and PCT -> 1200 mOsm in the bend (highest concentration) -> 100 mOsm at end of nephron loop to DCT (losing NaCl and water is trapped to dilute it, hypo-osmotic) Vasa Recta: 1&2&3. *descending limb* permeable to water and NaCl, water moves out of blood to ISF (vasa recta), NaCl moves into blood from ISF, both passive; *ascending limb* permeable to water and NaCl, water moves into blood from ISF, NaCl moves out of blood to ISF, both passive 4. start at efferent arteriole as isosmotic 300 mOsm, 1200 mOsm at bend of vasa recta, 325 mOsm going into vein
Internal anatomy continued
Minor calyces Drain pyramids at papillae Major calyces Collect urine from minor calyces Empty urine into renal pelvis Urine flow Renal pyramid minor calyx -> major calyx -> renal pelvis -> ureter
Urethra
Muscular tube that drains the bladder and conveys it out of the body Lining epithelium Mostly pseudostratified columnar epithelium, except Transitional epithelium near bladder Stratified squamous epithelium near external urethral orifice
Reabsorptive Capabilities of Renal Tubules and Collecting Ducts Part 2 (nephron loop)
Nephron Loop of Henle Descending limb - H2O can leave; solutes cannot Ascending limb - H2O cannot leave; solutes can (no aquaporins) (depends on transport proteins) Thin segment - passive Na+ movement out (down concentration gradient) Thick segment - Na+-K+ Pump (Active Transport) (out of filtrate)
Juxtaglomerular Apparatus (JGA)
One JGA per nephron - Important in regulation of filtrate formation (GFR) and blood pressure - Involves modified portions of the 1. Distal Convoluted Tubule 2. Afferent (sometimes efferent) arteriole *see print out picture*
Regulation of urine concentration and volume
Osmolality *Number of solute particles in 1 kg of H2O* Reflects ability to cause osmosis - "suck water" More solutes per water = more concentrated Osmolality of body fluids Expressed in milliosmols (mOsm) Kidneys maintain osmolality of plasma at ~300 mOsm by regulating urine concentration and volume Kidneys regulate with *countercurrent mechanism* - help with BP and blood volume
Reabsorptive Capabilities of Renal Tubules and Collecting Ducts Part 1 (PCT)
PCT *Site of most reabsorption* All nutrients, e.g., glucose and amino acids 65% of Na+ and water Many ions All uric acid; ½ urea (later secreted back into filtrate)
Tubular Secretion - From Blood to Filtrate
Reabsorption in reverse; almost all in DCT and collecting duct K+, H+, NH4+, creatinine, organic acids and bases move from peritubular capillaries through tubule cells into filtrate Eliminates undesirable substances passively reabsorbed (e.g., urea and uric acid) (it follows water gradient) Rids body of excess K+ (aldosterone effect) Controls blood pH by altering amounts of H+ or HCO3- in urine
Internal anatomy
Renal Cortex: Light colored, granular appearing superficial region Renal medulla: - Composed of cone-shaped medullary (renal) pyramids (*medullary tissue*) - Pyramids separated by renal columns; Inward extensions of *cortical tissue* Papilla Tip of pyramid; releases urine into minor calyx Lobe Medullary pyramid and its surrounding cortical tissue; ~8/kidney
Internal anatomy of kidney (ID)
See picture in book
Cell types
See picture in notes
Osmotic gradient in renal medulla
See picture in print out
three layers of the filtration membrane
See picture in slides - filtration membrane determines what passes out of blood into nephron 1. capillary endothelium 2. basement membrane 3. foot processes of podocyte of glomerular capsule
Loop of Henle: Countercurrent Mechanism
See print out
Summary of tubular reabsorption and secretion
See print out to fill in blanks
Urinary bladder information
Signal to urinate about 250 ml *May be painful or desperation set in at 500ml* Max capacity is 800-1000ml. If over-distended, may burst. Infant urinates 40x/day. At 2mos. 400ml/day compared to adults @ 1500ml/day
Urinary bladder layers
The bladder wall has three layers Transitional epithelial mucosa A thick muscular layer (Detrusor muscle) A fibrous adventitia The bladder is distensible and collapses when empty As urine accumulates, the bladder expands without significant rise in internal pressure
Extrinsic Controls of GFR - Renin-Angiotensin Mechanism (3 triggers)
Three triggers for the JGA (Renin Release) 1. Decline in blood pressure at the glomerulus - releases renin from granular cells (less stretch in arteriole walls sensed by baroreceptors) 2. Stimulation of JG cells by sympathetic innervation at granular cells - powerful vasoconstriction of afferent arteriole slows filtrate production and decreases GFR - releases renin 3. Decline in osmotic concentration (low Na+) of tubular fluid at the macula densa - signals granular cells to release renin
Extrinsic Controls of GFR - Sympathetic Nervous System
Under normal conditions at rest Renal blood vessels are dilated Renal autoregulation (intrinsic) mechanisms prevail
High osmolality of medullary fluid?
Urea + countercurrent multiplication
Effects of Urea
Urea contributes to *high osmolality* in medulla Deep region of collecting duct (mainly papillary duct) is permeable to urea *see picture in print out*
Role and movement of Urea
Urea enters from filtrate of blood, leaves at deep collecting duct/papillary duct which is permeable to urea so it contributes to interstitial fluid osmolality and then recirculates; small part will reenter at the thin ascending limb of nephron loop, comes into filtrate, facilitated diffusion (passive) Urea contributes to the concentration gradient used in the vasa recta by increasing osmolality of ISF
The countercurrent exchanger
Vasa recta Preserve medullary gradient Prevent rapid removal of salt from interstitial space (recirculates)! Remove reabsorbed water from the kidney! Water entering ascending vasa recta either from descending vasa recta or reabsorbed from nephron loop and collecting duct Volume of blood at end of vasa recta greater than at beginning *see print out* *know this printout!!!*
primary active transport of Na+ occurs in proximal convoluted tubule cells where?
basolateral membrane (Na+/K+ pump)
Differ between cortical and juxtamedullary nephrons
cortical: short nephron loop glomerulus is further from cortex-medulla junction efferent arteriole supplies peritubular capillaries juxtamedullary: long nephron loop glomerulus closer to cortex-medulla junction efferent arteriole supplies vasa recta
why glucose in urine means diabetes mellitus?
glucose occupies all transport carriers and it is no longer reabsorbed (enters filtrate via filtration and is not secreted)
Renin-angiotensin mechanism is mainly to do what?
increase BP and water conservation
vasa recta are associated with ?
juxtamedullary nephrons
urine forming units?
nephrons
urine is collected where?
pelvis
The filtration membrane is?
permeable to all substances smaller than 3nm (not highly selective)
sectional view of kidney showing major arteries and veins
see picture in slides
Representative Nephron/ Nephron anatomy
see powerpoint
Countercurrent Multiplication and Concentration of Urine
see print out
Long nephron loops of juxtamedullary nephrons create the gradient
see print out (2) *know this!!!*
Summary of Nephron Function
see print outs (2)
composition of filtrate in capsular space?
similar to plasma only no proteins
renal tubule: what is inhibited if simple squamous is damaged?
thin segment of nephron loop
regulation of water output
total daily water loss ~ 2500 ml/day obligatory water loss ~ 400-500 ml/day regulated water loss