Lecture 2 (urinary) -EXAM 5 Flashcards
Kidneys perform a number of key functions:
* What does it regulate? (4)
- regulate osmolarity of body fluids by urine water and solute concentrations
- regulate plasma concentrations of Na+, K+, Ca2+, Mg2+, Cl−, HCO3−, phosphate, and sulfate
- regulate the volume of the extracellular fluid by controlling Na+ and water excretion.
- regulate arterial blood pressure by adjusting Na+ excretion and producing various substances (e.g., renin) that can affect blood pressure.
Kidneys perform a number of key functions:
* What does it play an essential role in?
* What does it eliminate?
* What does it remove?
- play essential role in acid–base balance by altering renal H+ excretion and HCO3− reabsorption.
- eliminate the waste products of metabolism, including urea (the main nitrogen-containing end product of protein metabolism in humans), uric acid (an end product of purine metabolism), and creatinine (an end product of muscle metabolism).
- remove many drugs (e.g., penicillin), drug metabolites, and foreign or toxic compounds.
Kidneys perform a number of key functions:
* The major site of what?
* Degrades what?
* What does it synthesize? (2)
- major sites of production of certain hormones, including erythropoietin and vitamin D3
- degrade several hormones, including insulin, glucagon, and parathyroid hormone.
- synthesize ammonia, which plays a role in acid base homeostasis
- synthesize substances that affect RBF and Na+ excretion, including arachidonic acid derivatives (prostaglandins and thromboxane A2) and kallikrein (a proteolytic enzyme that results in the production of kinins).
When the kidneys fail, a host of problems ensue. What is used to help?
Dialysis and kidney transplantation are commonly used treatments for advanced (end-stage) renal failure.
Kidneys are highly what?
highly vascular & innervated
Kidneys:
* Recieve how much CO?
* What are the vessels?
* Richly innervated by what? What does this cause (3)
receive ~20% CO
single renal artery > anterior and posterior branch divisions > five segmental arteries
richly innervated by sympathetic nerve fibers who stimulation causes:
* constriction of renal blood vessels and a decrease in renal blood flow (RBF)
* increase in Na+ reabsorption by a direct action tubular cells
* Renin release
Afferent (sensory) renal nerves are stimulated by what?
mechanical stretch or by various chemicals in the renal parenchyma.
Explain the breakout of the arteries and veins of the kidney
* What do you change in order to affect flow?
What is the functional unit of kidney? Explain the structure and how many are in one kidney?
Nephron-> 1 mill/kidney
How is vascular system different in cortical nephron and juxtamedullary nephron?
- Cortical: only peritubular capillaries
- Jux: peritubular cap. and vasa recta
What are the macula densa cells, mesangial cells and granular cells?
- Macula densa cells (chemoreceptors): monitor the composition of the fluid in the tubule lumen-> located in DCT or some books say loop of henle
- Mesangial cells: transmit information from macula densa cells to the granular cells
- Granular cells: modified vascular smooth muscle cell; synthesize and release renin
What is the equation for excreted?
Excreted= filtered-reabsorbed +secreted
Urine formation involves what three basic processes?
- Glomerular filtration: 20% plasma filtered, remaining 80% flows through the efferent arteriole and into the peritubular capillaries. ~180 L of plasma is filtered per day; body plasma volume filtered 65 times per day.
- Tubular reabsorption: ~178.5 L is reabsorbed. Remaining 1.5 L is excreted as urine. Reabsorbed substances include many important ions (e.g., Na+, K+, Ca2+, Mg2+, Cl−, HCO3−, and phosphate), water, important metabolites (e.g., glucose and amino acids)
- Tubular secretion: route for a substance to enter the renal tubules. Mechanism for selectively eliminating substance from the plasma
The functional state of these urine formation processes can be evaluated using several tests based on what?
renal clearance concept
NOTES
- Glomeruli of cortical nephrons are located where? What are their loops of henle like?
- JM nephrons have glomeruli located where? Waht are their loop sof henle like?
- JM nephrons are what?
- When effective circulating blood volume is reduced, a higher proportion of renal blood flow (RBF) is directed to what?
- Glomeruli of cortical nephrons are located in the outer cortex and the loops of Henle are short.
- JM nephrons have glomeruli located deep in the cortex and have long loops of Henle, many extending to the tip of the renal papilla.
- JM nephrons are “salt conserving” and are important for urine concentration.
- When effective circulating blood volume is reduced, a higher proportion of renal blood flow (RBF) is directed to JM nephrons, helping to conserve extracellular fluid (ECF) volume.
Glomerular filtration rate is primarily what?
- primarily a physical process and does not involve intracellular pumps (no active transport)
- Major force is hydrostatic pressure of blood
What are the three layers of the glomerular fitration barrier?
- Endothelium: Pores too large to restrict the passage of the smaller plasma proteins.
- Basement membrane: Negatively charged so repels plasma proteins (since proteins are usually - charged)
- Visceral layer of the Bowman capsule: Podocytes, filtration slit, slit diaphragm, meshlike barrier, filtration of small proteins.
What is ultrafilrate, filtered and non-filtered?
- Ultrafiltrate: filtration of small molecules but restricts the passage of macromolecules
- Filtered: low molecular weight substances that are freely dissolved in plasma and includes various polar organic molecules such as glucose, amino acids, ions peptides, drugs, and waste products (e.g., creatinine and urea).
- Non-filtered: blood cells, large proteins (Proteinuria is the hallmark of glomerular filtration barrier disorder.)-> if damaged to membrane protein will be in urine which is not good
What is the effect of molecular size of the glomerular filtration of macromolecules? Inulin?
- hemoglobin and albumin are just large enough to avoid filtration at normal glomeruli on the basis of their size
- Inulin: is not reabsorbed or secreted so can measure the rate of clearance
What is the effect of electrical charge on glmerular filtration of macromolecules
filtration of negatively charged macromolecules (but not small anions) is reduced.
Glomerular hemodyamic forces:
* Characterized by what?
* GFR depends on what?
* Average capillary hydrostatic pressure in glomerulus much is what compared to skeletal muscle?
* Capillary hydrostatic pressure declines little because why?
* At efferent end, an increase in COP opposes what?
- Characterized by high capillary pressure and low vascular resistance
- GFR depends on Starling forces - balance of hydrostatic & colloid osmotic pressures
- Average capillary hydrostatic pressure in glomerulus much higher than skeletal muscle (55 vs 25 mmHg)
- Capillary hydrostatic pressure declines little because glomerulus contains many (30 to 50) capillary loops in parallel = low resistance to blood flow
- At efferent end, an increase in COP opposes the outward movement of fluid.
Using the pictures, explain the difference between skeletal and glomerular capillary?
Why is the glomerular filtration hight?
the glomerular capillary blood is exposed to a large, porous surface and there is a high transmural pressure gradient favoring filtration.
What creates a high capillary hydrostatic blood pressure to drive filtration?
Having an arteriolar resistance vessel at the distal end of the glomerular capillary instead of a venule creates
RBF is affected by what? (3)
1) hormones,
2) extrinsic neural stimulation
3) local regulatory factors.
Autoregulation of RBF:
* Maintains a constant blood flow during what?
* RBF kept relatively constant when perfusion pressure is varied btw what?
* When the perfusion pressure is raised, what happens? Lowered?
* When MAP is between 80 and 180 mmHg the Glomerular Filtration Rate (GFR) is what?
* When does the GFR cease?
- Maintains a constant blood flow during changes in mean arterial pressure
- RBF kept relatively constant when perfusion pressure is varied from 80 to 180 mm Hg
- When the perfusion pressure is raised the renal arterioles constrict, when lowered they dilate, thereby maintaining a constant blood flow and capillary pressure.
- When MAP is between 80 and 180 mmHg the Glomerular Filtration Rate (GFR) = 125mL/min
- GFR ceases at MAP < 50 mm Hg
Optimal renal blood flow is maintained by what?
- Optimal renal blood flow is maintained by autoregulation (intrinsic/local)
What are the two renal intrisic autoregulation mechanism?
Myogenic and tubuloglomerular feedback mechanism
What is the myogenic mechanism?
- increase in pressure stretches the afferent arteriolar walls which then activate stretch-activated cation channels in the arteriolar smooth muscle cells.
- this causes intracellular Ca2+ to rise, resulting in, smooth muscle contraction
- a reduction in vessel lumen diameter which increase resistance/decreased flow
- Counteracts the effect of high perfusion pressure, which would otherwise have increased RBF.
What is the tubuloglomerular feedback mechanism.
When single-nephron glomerular filtration rate (GFR) is increased—for example, because of an increase in arterial blood pressure—more NaCl is delivered to and reabsorbed by the macula densa, leading to constriction of the nearby afferent arteriole. This negative feedback system plays a role in autoregulation of renal blood flow and GFR.
What are the three ways of renal extrinsic regulation?
- Sympathetic nerve stimulation
- hormones/chemicals
- Renal protective mechanism
For renal extrinsic regulation: how does sympathetic nerve stimulation work/do?
- Vasoconstriction of afferent or efferent arteriole = decrease in RBF.
- Activated under stressful conditions - cold temperatures, deep anesthesia, fearful situations, hemorrhage, pain, and strenuous exercise.
- In these conditions, viewed as an emergency mechanism that helps increase TPR, MAP, CO
For renal extrinsic regulation, what hormones/chemicals vasodilate and vasoconstrict?
- Kidney vasoconstrictors:adenosine, angiotensin II, endothelin, epinephrine, norepinephrine, ADH
- Kidney vasodilators: atrial natriuretic peptide, dopamine, histamine, kinins, nitric oxide, and prostaglandins
For renal extrinsic regulation, what is the renal protective mechanism?
- A sustained increase in sympathetic nerve activity or plasma angiotensin II concentration stimulates the production of renal vasodilator prostaglandins.
- These prostaglandins oppose the pure constrictor effect of chronic sympathetic nerve stimulation or angiotensin II, such as that seen in chronic heart failure.
- Prevents too severe a reduction in RBF in chronic pathological conditions that could cause renal damage.
What profoundly affect the GFR?
Changes in glomerular capillary hydrostatic pressure
Explain the reabsorption and secretion of the different areas in the renal tube
Tubular absorption involves what?
involves diffusion and active transport
Where is water reabsored? Sodium?
WATER:
* all regions of the renal tubule. Exceptions are ascending limb of the loop of Henle and DCT and CD (unless alsosterone and ADH are secreted)
SODIUM:
* PCT ~65%
* loop of Henle 25%
* remaining DCT and CD (when aldosterone and ADH present)
Where is glucose and urea reabsorbed? What is urea dependent on
- GLUCOSE: PCT 100%
- UREA: PCT via passive transport. Urea reabsorption is dependent on the reabsorption of water in PCT
What is load dependence
increase in the filtered load of Na+ from the glomerulus stimulates an increase in sodium reabsorption by the tubule such that the percent of sodium reabsorbed remains the same. This phenomenon is called glomerulotubular balance
What are the characteritics of the PCT?
Over 70% of filtered solutes & water reabsorbed along what?
Along PCT: PCT responsible for reabsorbing all of the filtered glucose and amino acids, and reabsorbs the largest fraction of the filtered Na+, K+, Ca2+, Cl−, HCO3−, and water and secretes various organic anions and cations.
What is essential for sodium reabsorption? Explain
Active Na+/K+-ATPase pump is essential for sodium reabsorption.
* All sodium transport is dependent on the sodium ATPase pumps in the basolateral membrane.
* Sodium reabsorption across the apical membrane is accomplished through Na to solute cotransporters, H+- driven sodium reabsorption, and paracellular Cl–-driven sodium transport.
* Glucose, amino acids, phosphate, and numerous other substances are transported by separate carriers.
What are the characteristics of DCT and collecting duct?
Small amounts of water and sodium are reabsorbed where? What can cause a major increase?
- Small amounts of water and sodium are reabsorbed in the DCT and Collecting Duct.
- However, ion and water transport in the DCT and collecting ducts can be dramatically increased by presence of certain hormones.
What does aldosterone do?
Aldosterone increases Na+ reabsorption as well as K+ and H+ secretion with the secretory effects primarily occurring in the connecting ducts and cortical region of the collecting ducts.
What does ADH do?
Arginine vasopressin, also called antidiuretic hormone (ADH) increases water permeability in the collecting ducts
What are the two type of cells + what do they do in late distal tubule and collecting duct?
TUBULE SECRETION:
* The most important constituents secreted are what?
* PCT secretion eliminates what?
* Distal part of DCT and CD are the primary site for what?
- The most important constituents secreted are H+, K+, and Cl−.
- PCT secretion eliminates many toxins and drugs from the blood.
- Distal part of DCT and CD are the primary site for K+ secretion.
- In PCT, water reabsorption was what?
- In LoH, water reabsorption is not what?
- In PCT, water reabsorption was obligatory (water followed the solutes).
- In LoH, water reabsorption is not automatically coupled to reabsorption of solutes.