OS II Exam 1 Flashcards
- Where is the kidney located?
GROSS ANATOMY OF THE KIDNEY Position of Kidney • Deep to 12th rib: • Left kidney slightly higher than the right • Perirenal fat Blood Supply: Renal Arteries & Veins
- Describe the urine collection system from minor calyces to the ureter.
Internal structure • Cortex • Medulla • Urine excreted through papillae into calyces Urine passages • Minor calyces • Major Calyces • Renal pelvis • Ureter carries urine down to bladder
- What makes up a nephron? What are the different parts of the tubule? What is the papilla? What is the glomerulus?
- What makes up a nephron? What are the different parts of the tubule? What is the papilla? What is the glomerulus?
Nephron: the functional unit of the kidney • Glomerulus (capillaries) • Tubule: proximal convoluted tubule, loop of Henle, distal convoluted tubule. collecting tubule/duct -> papilla • Convoluted tubules in cortex • Loops of Henle and collecting tubules/ducts in medulla Aging kidney • 1 million nephrons in each kidney; decrease in number with age • After 40, number decreases 10% every 10 years; only 40% are functional by age 80
- Describe the relationship of the glomerulus to Bowman’s capsule.
- Describe the relationship of the glomerulus to Bowman’s capsule.
Renal corpuscle: Glomerulus and Capsule
Glomerulus
• Capillaries loops invaginate Bowman’s capsule
Bowman’s capsule
• Proximal end of tubule forms bursa around
capillaries: visceral and parietal layers
• Filtration barrier
- Differentiate between the two types of nephrons.
- Differentiate between the two types of nephrons.
Tubule
Proximal convoluted tubule
• Reabsorption of water,
electrolytes, glucose, etc.
• Secretion
Loop of Henle: descending / ascending
Distal convoluted tubules &
Collecting tubule and ducts
• Fine tuning of reabsorption
• Several collecting tubules drain
into a collecting duct
• Urine concentration
Superficial (cortical) nephrons
• Short loops of Henle
• Reabsorption and secretion
Juxtamedullary nephrons
• Long loops of Henle
• Concentration of urine
Tubular epithelium histolog
- Characterize the structure and transport mechanisms of tubular cells. Differentiate the convoluted tubules from the loops of Henle
- Characterize the structure and transport mechanisms of tubular cells. Differentiate the convoluted tubules from the loops of Henle
Tubules:
Proximal convoluted tubule
- Reabsorption of water, electrolytes, glucose, etc.
- Secretion
Loop of Henle: descending / ascending
Distal convoluted tubules &
Collecting tubule and ducts
- Fine tuning of reabsorption
- Several collecting tubules drain into a collecting duct
- Urine concentration
Tubular epithelium histology
- Proximal, distal and collecting tubules: simple cuboidal and columnar cells; large surface area for transport of water, ions and nutrients
- Thin loop of Henle: simple squamous epithelium
- Describe the vasculature of the kidneys: the arterial branches, capillary beds
- Describe the vasculature of the kidneys: the arterial branches, capillary beds
The renal vasculature takes up 21% of cardiac output. Single or double renal arteries branch from the aorta, and lobar (or segmental) arteries branch into interlobars that extend between the pyramids. Arcuate arteries are located on the basal (outter part) of the pyramids, and give off interlobular arteries. The interlobular arteries give rise to the afferent arterioles, which lead to the glomerular capillaries, and then contine to the efferent arterioles, peritubular capillaries, and vasa recta.
- What is the juxtaglomerular apparatus? What are macula densa cells?
- What is the juxtaglomerular apparatus? What are macula densa cells?
The JGA apparatus is where the TAL (thick ascending loop), afferent arteriole, and DCT (distal convoluted tubule) meet. The macula densa cells (which line part of the distal convoluted tubule) regulate the afferent arteriole by responding to osmolar levels of Na/Cl. The juxtaglomerular cells in the afferent arterioles respond by changing contraction or releasing renin in the blood.
- Describe the sympathetic innervation of the kidney
- Describe the sympathetic innervation of the kidney
The kidney is sympathetically innervated by preganglionic neurons from T12 and L1. Also, postganglionic neurons in the renal ganglion project to the kidney for vasoconstriction and hormone secretion.
- Renal blood flow is maintained homeostatically. Why?
- Renal blood flow is maintained homeostatically. Why?
Renal blood flow is maintained high enough to ensure precise regulation of body fluid volumes and solute concentrations, but slow enough to reabsorb indispensable constituents, such as Na
- Describe the structure and function of the filtration barrier. What are the two factors that determine whether a molecule passes through the barrier?
- Describe the structure and function of the filtration barrier. What are the two factors that determine whether a molecule passes through the barrier?
Hydrostatic blood pressure filters blood from the glomerulus through the filtration barrier to Bowman’s capsule. 21% of cardiac output (180 L/day) is filtered, and 99% of this is reabsorbed. The filter is made up of 1. capillary endothelium, 2. glomerular basement membrane (basal lamina), and 3. slide diaphragms between podocyte foot processes (visceral layer of Bowman’s capsule).
Molecule size & charge determine whether it will pass through the barrier. Cells and large & medium proteins are restricted from filtration, and negatively charged proteins are repelled as well.
- In the formula for glomerular filtration, what is Kf? What is the net filtration pressure?
- In the formula for glomerular filtration, what is Kf? What is the net filtration pressure?
Kf = glomerular capillary filtration coefficient.
Also note: GFR (Glomerular Filtration RAte) = Kf x NFP (Net Filtration Pressure). Also, constriction of mesangial cells (pericytes) reduces capillary surface area, decreases Kf, and lowers the Glomerular Filtration Rate.
Net Filtration Pressure (NFP) = Outward Pressure - inward pressure
NFP = HPgc - (HPcs + OPgc)
NFP = Glomerular Capillary pressure - plasma oncotic pressure - Bowman’s capsule hydrostatic pressure
The Net filtration pressure is the balance between hydrostatic and oncotic pressure across the filtration barrier.
- What impact does break down of the filtration barrier have on protein levels in the blood? What are the systemic consequences of this?
- What impact does break down of the filtration barrier have on protein levels in the blood? What are the systemic consequences of this?
Proteinuria (excess excretion of proteins) causes a decreased glomerular filtration rate, but increased protein filtration. Podocyte alterations reduce the total number of fenestrations (reduces GFR), but slight increases in large pores still generates significant loss of proteins
In nephrotic syndrome (which is part of nephropathy), glomeruli increase their permeability to proteins (proteinururia). Low plasma levels of proteins can lead to edema, hypovolemia, and oliguria (reduced urination). Why? Starling Forces!!!!
Note!
- Distinguish between paracellular and transcellular transport of water and solutes
- Distinguish between paracellular and transcellular transport of water and solutes
Paracellulary transport (across epithelium between cells) is determined by tight junctions. Transcellular transport (through a cell) is determined by Na/K pumps and passive transporters & aquaporins.
- What is secondary active transport?
- What is secondary active transport?
Secondary active transport is a form of active transport across a biological membrane in which a transporter protein couples the movement of an ion (typically Na+ or H+) down its electrochemical gradient to the uphill movement of another molecule or ion against a concentration/electrochemical gradient. Thus, energy stored in the electrochemical gradient of an ion is used to drive the transport of another solute against a concentration or electrochemical gradient.
In secondary active transport, active transport of Na+ created Na+ gradient that passively cotransports other solutes on carriers such as sodium-dependent organic glucose transporters (SGLT).
- What are aquaporins?
- What are aquaporins?
Aquaporins are membrane proteins permeable to water, found in most tissues. The cell permeability to water depends on up or down regulation of aquaporins. Aquaporin transcellular transport of water dominates throughout the tubule, and aquaporins play a role in reabsorption.
- Where in the tubule are water and Na reabsorbed? Where does most of it occur?
- Where in the tubule are water and Na reabsorbed? Where does most of it occur?
NaCl& WATER
Reabsorption occurs throughout tubule
Note how Na + and water are reabsorbed either together or separately
NaCl & water together
- Proximal convoluted tubule (2/3)
- Distal convoluted tubule
NaClonly
- Ascending loop of Henle
- Collecting tubule
Water only
- Descending loop
- Collecting duct (variable amount; aquaporinsregulated by ADH, see below)
- What impact does extracellular hypertonicity have on cell size? Hypotonicity
- What impact does extracellular hypertonicity have on cell size? Hypotonicity
HypERtonic - Cell SHRINKS as water rushes out
HypOtonic - cell swells as water rushes in
- How does the interstitial region of the medullary pyramid become hypertonic? What substances are used? How is the Hypertonicity protected by the vasa recta?
- How does the interstitial region of the medullary pyramid become hypertonic? What substances are used? How is the Hypertonicity protected by the vasa recta?
Hypertonicity of the medullary interstitium provides the motivation (osmotic force) for water reabsorption in the collecting ducts (Note: ADH gives permission via water permeability in collecting tubules).
Interstitial accumulation of urea and NaCl create interstitial medullary gradient of hypertonicity.
Urea enters the interstitium via the collecting duct;
NaCl enters (1) passively from the thin ascending loop, and (2) actively from the thick ascending loop.
The water and solutes become suspended in the interstitium by forming a gel with
hyaluronic acid and albumin.
- How does ADH regulate osmolarity? Where and what are the osmoreceptors? Where does ADH act and what are its actions? What stimulates ADH release? Where does thirst come into this
- How does ADH regulate osmolarity? Where and what are the osmoreceptors? Where does ADH act and what are its actions? What stimulates ADH release? Where does thirst come into this?
ADH (anti-diuretic hormone) regulates osmolarity by controlling water permeability in collecting tubules via aquaporins (permission for water reabsorption).
ADH = vasopressin (VP) + arginine vasopressin (AVP)
Up-regulates aquaporins in collecting ducts (capillaries readily reabsorb water)
Note: “Anti-diuretic” means it causes water to be held in, and thus you urinate less frequently. Diuretics do the opposite.
ADH is synthesized in the hypothalmic paraventricular (PV) & supraoptic (SO) neurons; it is then transported along axons into the posterior pituitary and secreted into circulation.
Osmoregulatory feedback loop: Increased blood osmolarity stimulates osmoreceptors in hypothalamus → ADH released from posterior pituitary → ADH triggers water reabsorption and dilution of excess osmolarity
Osmoreceptor cells in the anterior hypothalamus (OVLT) project to SO/PV nuclei to trigger the release of ADH; they also project to the thirst and drinking regions of the limbic system.
Increased plasma Na+ (food) shrinks osmoreceptor cells, triggering AP and increased ADH release; water is reabsorbed
Decreased plasma Na+ (drink water) expands osmoreceptors decreasing ADH release; water is excreted; short latency
Nausea, nicotine & morphine stimulate ADH release (less urination). Alcohol inhibits ADH release (more urination).
- Describe tubuloglomerular feedback in terms of what triggers it, how it works and what is its outcome? What role do the macula densa cells play? Juxtaglomerular cells
- Describe tubuloglomerular feedback in terms of what triggers it, how it works and what is its outcome? What role do the macula densa cells play? Juxtaglomerular cells?
Tubuloglomerular feedback
Homeostatic mechanism to prevent excess or deficiency of RBF & GFR
Increased RBF & GFR enhances fluid flow
Macular detection of Cl- increases afferent arteriole resistance
Decreased blood entry into glomerulus reduces RBF & GFR
Opposite effect with decrease in RBF/GFR
Increased GFR & RBF enhances tubular fluid flow
FLOW RECEPTORS in macula densa cells detect high levels of Cl- & stimulate Na/K/Cl transporters
Macula densa cells release ADENOSINE which constricts afferent arteriole: restore RBF and GFR
Note how NaCl, not water, levels were used to regulate RBF and GFR.
Juxtaglomerular cells (JG) release renin:
Reabsorption
- Describe the Starling forces involved in regulating the amount of reabsorption. Contrast the hydrostatic and oncotic pressures in the tubule and vasa recta
Reabsrorption
- Describe the Starling forces involved in regulating the amount of reabsorption. Contrast the hydrostatic and oncotic pressures in the tubule and vasa recta.
Reabsorption occurs when:
Capillary hydrostatic pressure is lower than that of the tubule
20% of fluid has been filtered
Capillary oncotic pressure is higher than that of the tubule
higher concentration of proteins since they were not filtered out
Fluid flows down hydrostatic and oncotic gradients from tubule and interstitial fluid into the capillary
Starling forces provide MOTIVATION for reabsorption
- How does the efferent arteriole impact reabsorption
- How does the efferent arteriole impact reabsorption?
Proportion of plasma filtered is determined by constriction of the efferent arteriole (see above). Reabsorption is guided by amount of blood flow in efferent arteriole and vasa recta (constriction → reabsorption of Na+ & water; dilation → excretion of Na+ & water).
- Describe angiotensin II: its trigger, source, synthetic pathway, action. What is renin and where does it arise? What are the actions of angio II on renal vasculature and tubule
- Describe angiotensin II: its trigger, source, synthetic pathway, action. What is renin and where does it arise? What are the actions of angio II on renal vasculature and tubule?
Angiotensin II: increases blood volume/pressure by promoting reabsorption of Na+ & water
trigger: upregulation of renin/ACE (for example, decrease in renal perfusion by JGA
stimulates production of renin, wich catalyzes formation of Angio I)
source: liver
synthetic pathway:
synthesized in steps by the enzymatic actions of RENIN & ACE:
action (renal vasculature/tubule): (1) stimulates renal reabsorption directly and aldosterone & ADH; (2) general vasoconstriction; (3) increases sympathetic activity
Renin: a protease released from JG cells by (1) drop in BP, (2) drop in blood volume, or (3) sympathetic nervous system activity.
source: juxtaglomerular cells (JG
- Describe the sympathetic function in the kidney: trigger, action
- Describe the sympathetic function in the kidney: trigger, action
SYMPATHETIC ACTIVITY
Triggered by drops in systemic blood pressure or emotions such as fright.
Aortic and carotid baroreceptors detect drops in arterial pressure and stimulate hypothalamus via 9th & 10th (vagus) cranial nerves
Hypothalamus triggers sympathetic activity
Brain stem centers activate sympathetic neurons
– Preganglionic neurons innervate prevertebral ganglia
– Postganglionic neurons innervate arterioles, JGA cells and tubular cells
Sympathetic activity facilitates water and sodium reabsorption:
Constrict afferent arterioles to reduce RBF, GFR
Stimulate renin release
Stimulate sodium reabsorption directly in proximal tubule cells
Constrict efferent arterioles and vasa recta to promote sodium and water reabsorption via Starling forces
Sympathetic responses occur more in defense reaction, exercise, or severe hemorrhage where its short latency can be beneficial
Response latency and durations:
– Neural → seconds
– Angiotensin II → minutes
- Describe aldosterone: trigger, source, action, time frame compared to sympathetic activity / angio II.
- Describe aldosterone: trigger, source, action, time frame compared to sympathetic activity / angio II.
Aldosterone: principal regulator of Na+ absorption, acts on distal tubule & collecting ducts
trigger: aldosterone is released in response to (1) antiotensin II (due to drop in BP), and (2) High K+ levels in blood.
source: aldosterone is a mineralocorticoid steroid hormone secreted by outer zona glomerulosa of the adrenal cortex.
action: up regulates Na+ chanels (ENaC channels), Na/K ATP-ases/pumps, and ATP levels in principal cells of distal tubule and collecting tubule to increase Na+ reabsorption and K+ secretion; promotes sodium and water reabsorption to restore volume; fine-tunes Na+ levels.
time frame: Much longer than angio II (see picture)
- What are the different mechanisms that inhibit reabsorption including ANP and pressure natriuresis
- What are the different mechanisms that inhibit reabsorption including ANP and pressure natriuresis?
Neuroendocrine factors & processes that decrease reabsorption and increase excretion in response to an increase in blood volume/pressure:
Decrease RAAS activity:
RAAS activity is decreased by processes that inhibit renin release in response to increased systemic pressure.
Increased NaCl levels in distal tubule
Decreases sympathetic activity
Increased pressure in afferent arteriolar baroreceptors
Natriuretic peptides:
Atrial Natriuretic Peptide (ANP): from atrium
Brain Natriuretic Peptide (BNP): from heart ventricle
Urodilatin: from distal tubules and collecting ducts in kidneys
Others: guanylin (intestines), cardiac steroids (adrenal & hypothalamus)
Excrete excess Na/water:
Increase GFR by dilating the afferent arteriole
Inhibit Na+ reabsorption by inhibiting Na+ channels
Inhibit H2O reabsorption by reducing ADH release
Inhibit secretion of renin & aldosterone
ANP deficits related to salt sensitive hypertension
Natriuretic peptides are released from atria and ventricles by increased venous volume/pressure & act on the brain
Pressure natriuresis:
Increases urinary excretion of Na+ & water only in response to an increase in blood volume
Plays major role in long-term BP regulation
Elevated renal perfusion pressure inhibits Na+ & water reabsorption by these actions
Increases GFR within autoregulatory limits
Down regulation of Na+ channels and Na+/K+ pumps in proximal tubule cells by endocytic removal
NO vasodilation shifts Starling forces to reduce reabsorption
Pressure natriuresis maintains an equilibrium point for salt levels (graphs on slide #36)
- What is the relationship between pressure natriuresis and NO?
- What is the relationship between pressure natriuresis and NO?
NO vasodilation shifts Starling forces to reduce reabsorption. Increased perfusion (shear stress) in vasa recta stimulates release of NO to reduce Na+ and water reabsorption. NO vasodilates vasa recta (pericytes). Increased capillary hydrostatic pressure inhibits NA and water reabsorption
