Renal Physiology

Question	Answer
Multilobular kidney species eg	Cattle
Unilobular kidney species	Horses, dogs, cats
Uropoiesis	Process of urine production. 1000-2000 L of blood flow through kidneys daily, yet only 1-2 L of urine excreted
Functions of kidney	1) Filter the blood (and produce urine), excrete metabolic waste (eg urea), retrieve filtered substances needed by body (low MW proteins, water, electrolytes), specifically alter rate of absorption/secretion according to body's needs. 2) Produce hormones that regulate BP (renin) and RBC production (erythropoietin)
Functional Unit of the Kidney	Nephron
2 types of nephrons	Cortical nephron and juxtamedullary nephron
Renal Vascular Supply	25% of CO flows to kidneys. Renal artery: enters kidney at hilus. Renal veins: leaves kidney at hilus. BUT more complicated than this (nephrons!)
Nephron Blood Flow	Renal artery-->arteries -->arterioles-->afferent arteriole-->glomerulus-->efferent arteriole -->peritubular capillaries+ Vasta Recta-->Venules-->Veins-->Renal Veins
Functions of the Nephron	Filtration Reabsorption Secretion Excretion
Filtration (1st step)	Passive transport process by which hydrostatic pressure forces liquid through a membrane. kidney: filtration occurs in glomerulus. Hydrostatic pressure = beating heart/BP. Membrane = glomerular capillaries. ~20% of plasma volume passing thru glomerulus at any given time is filtered. Entire plasma vol is filtered 60x/day
Glomerulus	1st step of renal function (filtration of blood). Occurs in glomerulus: network of capillaries that: 1)retain cellular components & medium-high MW proteins in vasculature 2)extrudes fluid (glomerular filtrate) almost identical to plasma in electrolyte and water composition (ultrafiltrate: same conc. of salts, glucose, bicarbonate, etc. as plasma does)
Glomerulus Structure	Afferent arterioles (A): Carry blood to glomerulus Glomerular capillaries (GC): water, solutes cross capillary wall into Bowman's space, forming glomerular filtration. Efferent arteriole (E) carries filtered blood from glomerulus
Glomerular Filtrate	Almost identical to plasma in electrolyte and water composition as well as containing sm molecules (urea, creatinine, glucose, sm plasma proteins). Contains waste products that must be cleared fr body as well as substances body doesn't want to lose in urine.
Tubular Reabsorption	Enables substances that need to be retained by body move back into blood stream (occurs primarily in proximal convoluted tubule and loop of Henle
Glomerular Filtration Rate	mL/min/Kg. One of most imp renal function parameters. Determined by: 1)net filtration pressure (how much hydrostatic pressure forcing fluid out) 2)filtration barrier permeability 3)area avail for filtration. Glomerular capillary walls create barrier to forces favoring and opposing filtration
Factors favoring Glomerular filtration	Hydrostatic pressure (force pushing it out) Oncotic pressure in Bowman's space (negligible) (protein->water magnets. Most not filtered out).
Factors opposing glomerular filtration	Plasma oncotic pressure (# of proteins in plasma; try to hold water in) Hydrostatic pressure in Bowman's space (decreases ability of hydrostatic pressure to force water out).
Net Filtration Pressure	Net filtration pressure decreases along capillary bed b/c loss of plasma vol along capillary bed->1)incr oncotic pressure 2)decreases hydrostatic pressure along capillary bed. Makes higher protein conc. as it moves along (water magnets)
Regulation of glomerular filtration rate	Normally maintained at a constant level despite changes in systemic BP. Regulated by systemic (extrinsic) and intrinsic factors. Renal effects on systemic BP and vol are regulated via humoral factors (eg. RAAS). Intrinsic control of glomerular capillary perfusion area mediated by: 1) myogenic reflex 2) tubuloglomerular feedback; 2 autoregulatory systems that control resistance of afferent and efferent arterioles
Permselectivity	Resposible for differences in the rate of filtration of blood components: 1) size: <2mn filtered (water, solutes) 2) net electrical charge: cation form filters more freely than neutral>anionic (eg albumin). Due to -ve charged glycoproteins in basal membrane, endothelial cells 3) shape and deformability of molecule: flexible molecules cross more readily than inflexible molecules (can elongate and get through pore)
Glomerular capillary wall	Structural & chemical characteristics establish permselectivity of the filtration barrier.
Activation of the Renin-Angiotensin-Aldosterone System (systemic factors in regulation of GFR)	Controlled by juxtaglomerular cells in kidney, which in response to decreased renal perfusion (due to decreased BP), release renin (enzyme) to incr renal perfusion. Renin converts angiotensin I to angiotensin II which stimulates adrenal gland to produce aldosterone. Angiotensin II also incr BP by causing vasoconstriction
Systemic Factors: Hormones that act to maintain blood volume	Hormones: I) angiotensin: enhance water and solute reabsorption (RAAS) ii) Antidiuretic Hormone (ADH/VP): enhance water and solute reabsorption (b/c too little blood vol). iii) atrial natriuretic peptide (ANP): promote natriuresis (excretion of Na+) and diuresis (excretion of water) (b/c too much blood vol) - atria; think atrial stretch receptors
Systemic Factors: Hormones that act to maintain vessel tone	Factors that affect vessel tone also affect systemic BP, renal perfusion, and filtration. eg VP, angiotensin II, and circulating catecholamines --> vasoconstriction --> Incr BP
Intrinsic Factors in the Regulation of GFR	Mechanisms within the nephron exert direct control of glomerular capillary perfusion
Intrinsic Factors in the Regulation of GFR 1) Myogenic Reflex	Intrinsic mechanism that exerts direct control of glomerular capillary perfusion. Immediate afferent arteriolar constriction after an incr in arteriolar wall tension. Immediate arteriolar dilation after a decrease in arteriolar wall tension leads to decrease and incr to blood flow in afferent arteriole, respectively
Intrinsic Factors in the Regulation of GFR 2) Tubuloglomerular Feedback	Juxtaglomerular cells secrete renin, and macula densa cells in wall of DT that detect incr in [NaCl] and secretes vasoconstrictor which acts on afferent arteriole to decrease GFR. Macula densa: incr [NaCl] in tubule fluid ->paracrine release of NO, adenosine, and ATP fr macula densa cells: decr renin release, incr resistance in afferent arteriole, decr glomerular capillary perfusion pressure. Together, cause decr GFR in indiv nephron->prevents tubule flow rates that exceed tubule transport capacity, preventing excess fluid and solute loss
Juxtaglomerular Apparatus	Distal tubule: associated w glomerulus of same nephron. Macula densa: cluster of epithelial cells located in distal portion of ascending loop of Henle Location of macula densa b/w afferent and efferent arterioles
Intrinsic Factors in the Regulation of GFR 3) Endolthelium COntrol	Contributes to local control of vascular tone by producing & releasing potent vasodilators & vasoconstrictors. Endothelium derived constrictiong factors incl: thromboxane A2 and Angiotensin II. Endothelium derived relaxing factors incl: NO (vasodilation), prostacyclin (metabolite of arachidonic acid), & prostaglandin E2 (metabolite of arachidonic acid). Local, act at indiv glomerulus to counteract systemic effects. Act really quickly b/c cross membrane quickly. Paracrine (influence at afferent arteriole)
Intrinsic Factors in the Regulation of GFR 3) Endothelium Control: Angiotensin II (AII)	Also stimulates production & release of vasodilative renal prostaglandins: Prostaglandin E2 & prostaglandin I2 (prostacyclin). Counteract vasoconstrictive effect of AII on the intrarenal vasculature which helps maintain renal vascular resistance at normal levels. (Otherwise generalized vasoconstriction by AII would cause decr renal blood flow and GFR despite incr systemic BP
(Reabsorption) Path of Filtrate Through Nephron	Bowman's capsule -> Proximal Convoluted Tubule (PCT) (most filtration here)-> Loop of Henle -> Distal Convoluted Tubule -> Collecting ducts Filtrate is modified as it moves through tubular system
Renal Tubule	Reabsorbs filtered substances (rate of reabsorption and secretion varies among segments of renal tubule). BUlk of filtrate formed in glomerulus must be reabsorbed in renal tubules. 100% of glucose reabsorbed into bloodstream. Amount of water we get rid of depends on body's state
Fractional Excretion Rate	% of a filtered substance that is excreted in the urine. Net result of tubular reabsorption and secretion of filtered substances
Proximal Tubule	Reabsorbs bulk (60%) of filtered substances. Structure of proximal tubule (++ mitochondria, BB, BL infoldings) & proximity to peritubular capillary facilitate high vol movement of substances in tubular fluid to brain. 2 pathways for movement: 1) Transcellular pathway 2) Paracellular pathway
Transcellular Pathway	Substances transported, cross the apical plasma membrane and discharge across BL plasma membrane into interstitial fluid on blood side of cell. Passage across apical and BL plasma membrane occurs via carrier mediated transport. BB: incr apical surface area for transport. Infoldings of BL membrane incr surface area for transport fr cell to interstitial fluid that bathes peritubular capillary
Paracellular Pathway	Substances cross fr tubular fluid across the zona occludens that attaches the proximal tubule cells to each other at the junction of the apical and BL membranes. Occurs by passive diffusion or solvent drag (solvent moves w water).
Peritubular Capillary	Movement of water and solutes form interstitial fluid into bloodstream is aided by proximity of peritubular capillary. Originates at efferent arteriole, subdivides and wraps around basal aspect of the proximal tubule: has 1) high oncotic pressure (high draw of water) 2) low hydrostatic pressure (not forcing anything out). Favours fluid & solute uptake fr interstitium into the bloodstream. Fluid exiting efferent arteriole protein-rich (water magnets)
Reabsorption of Solutes in Proximal Tubule	Takes place by a # of transport mechanisms incl: passive diffusion, solvent drag, primary active transport, secondary carrier mediated transport. In PT, transport of substances fr tubular fluid to blood driven by active transport of Na+ by Na+K+ ATPase pump located in BL membrane (extrudes 3 Na+ & takes up 2 K+. Glucose, AA's, phosphate, organic anions enter cell by 2ndary active transport w Na+
Active Transport of Na+ in Proximal Tubule	Na+ wants in, pulls AA w it Na+ wants in, pulls glucose w it Cotransport: carries more than 1 thing Pull fr cytoplasm to blood b/c of gradient (cotransporters in BL). CL- diffuses across zona occludens down electrochemical gradient.
Reabsorption of Calcium and Potassium in Proximal Tubule	Both present in sm amounts in tubular fluid. Ca2+ reabsorption: 65% of filtered Ca2+ reabsorbed in distal PT. 90% via passive processes in paracellular pathway due to electrochemical gradient & solvent drag. K+ reabsorption: via passive mechanisms in paracellular pathway & via K+ channels in apical and BL membrane
Reabsorption of peptides and low MW protein in PT	Majority of filtered peptides are degraded to AA's & are reabsorbed via Na+ co-transport or via specific transporters. Low MW proteins (insulin, glucagon, parathyroid hormone) are taken up in apical membrane via carrier mediated endocytosis, taken to lysosomes where they are broken down into AA's which are then transported across BL membrane AA's<peptides<proteins
PT Secretes Organic Ions	PT secretes variety of organic ions (incl endogenous wastes and exogenous toxins/drugs) into tubular fluid: excreted in urine via carrier mediated process. Endogenous organic wastes incl: bile salts, creatinine, etc. Exogenous toxins/drugs incl: antibiotics, diuretics, morphine. Provides basis for UA, antibiotic tx in UTI's, delivery of diuretics to site of action (ascending limb of Loop of Henle)
Tubular Secretion	Many waste products in blood are not completely filtered by glomerulus. Tubular secretion allows a second chance for body to remove wate products fr blood to be disposed of in urine. Further modification of intial glomerular filtrate occurs by selective secretion of substances fr peritubular capillaries into distal convoluted tubule (DCT) and collecting ducts. Secreted substances incl H+, NH3+ (ammonia), & K+
RAAS diagram	Decreased renal perfusion -> incr renin -> incr angiotensin -> incr aldosterone -->direct vasoconstrictive effect and incr Na+ and water retension (reabsorption in kidney) --> blood pressure --> incr renal perfusion
Enzyme required to convert angiotensin I to angiotensin II	Angiotensin converting enzyme (ACE). Primarily in lung but also in kidney and organs
Loop of Henle: Descending (thin) limb	Low epithelium with few mitochondria and few infoldings (no active transport of solutes). Passive permeability function: roleinwater reabsorption (incr solute concin filtrate). No brush border: function doesn't need a lot of absorption and mitochondria (energy).
Ascending (thick) limb of the Loop of Henle	tall epithelium w lots mitochondria and basolateral membrane infoldings (active transport of solutes). Reabsorb Na+, K+, Cl-, Ca 2+, Mg 2+. Impermeable to water! Tubular fluid becomes very dilute (decreased solute concentration). Sodium/potassium pump creates concentration gradient for sodium movement
Ascending (Thick) limb of Loop of Henle	Solute transport. Sodium: active transport of Na+ K+ ATPase pump in BL membrane. K+, Cl-, Ca2+ fr luminal fluid through 2ndary active co-transport via sodium, potassium, chlorine co-transporter. Cl: diffuses along conc gradient through Cl channel in BL membrane. K+: exits cell along conc gradient thru K+ channel on apical and BL surface. K+, Cl, Ca2+, Mg2+: thru paracellular pathway along lumen-blood electrochemical gradient created by Cl absorption and K+ excretion
Distal Convolulted Tubule	Taller epithelium w lots of mitochondria. Also reabsorbs sodium, potassium, chlorine, calcium, magnesium. Impermeable to water. Reabsorption of salts w/out water in distal convoluted tubule: hypotonic tubule fluid. Imp component of fluid vol regulation which allows kidney to excrete excess water w/out salt, preventing plasma hypotonicity
Collecting Duct	Reabsorbs NaCl, secretes or reabsorbs K+. Begins w collecting segment which connects nephrons to collecting duct system. Initial collecting tubules converge and empty into cortical collecting duct, which descends thru cortex and medulla to papillary tip where tubule fluid (urine) discharges into renal pelvis. 2 main cell types: principle cell and intercalated cell
Collecting Duct: Principle Cells	Major cell type in initial collecting duct, cortical collecting duct, and outer medullary collecting duct. 2/3 of cells. Reabsorbs NaCl, secretes K+.
Principle cells: reabsorbs NaCl	Na+ actively transported by Na+K+ ATPase pump in BL membrane to interstitial fluid -> electrochemical gradient for Na+ uptake fr tubule fluid via Na+ channels. Cl moves along paracellular pathway due to electrical chemical gradient.
Principle Cells: Secretes Potassium	Actively pumped fr interstitial fluid into cell by Na+K+ ATPase pump in BL membrane->incr intracellular [K+] (> tubule and interstitial fluid)-> K+ exit via K+ channels into tubules & interstitial fluid. Net K+ secretion b/c 1)apical K+ channels more permeable than BL K+ channels 2) lumen-negative electrical potential favours secretion
Collecting Duct: Intercalated Cells	2nd cell type in cortical collecting duct and outer medullary collecting duct. Reabsorbs K+: K+ actively transported fr cytoplasm across apical membrane in exchange for H+ by a H+K+ ATPase pump (this pump also contributes to acidification of urine). Mechanism to de-acidify blood by excreting H+ ions (acidic incr in urine)
Calcium Reabsorption	Most filtered calcium reabsorbed by kidney (imp in regulated of systemic calcium balance). 65% reabsorbed in PT via paracellular pathway. 20% reabsorbed by ascending limb by both paracellular and transcellular pathways. 10% reabsorbed by distal convoluted tubule and connecting segment by active transcellular transport via Ca2+ ATPase pump, Na+/Ca2+ antiporter in BL membrane. 1-2% reabsorbed in collecting duct via unknown mechanism. Parathyroid hormone and calcitonin play imp role in controlling renal Ca2+ excretion
Aldosterone	Mineralcorticoid secreted by adrenal cortex in response to systemic hypotesion through renin-angiotensin system. Enhances 1)Na+ reabsorption 2)K+ secretion. How? 1) Na+ reabsorption 2) stimulate Na+K+ATPase pump activity. Released due to decreased BP. Incr blood K+ levels can also stimulate this
Na+ Reabsorption (Aldosterone)	acts on connecting segment cells and principle cells of collecting duct to 1)permeability of apical Na+ channels (Make Na+ move thru more freely) 2) stimulate Na+K+ ATPase pump activity (work harder pumpingmore Na+ out, incr conc gradient)
K+ Secretion (Aldosterone)	Aldosterone acts to stimulate Na+K+ ATPse pump activity which decreases serum K+ by moving K+ fr extracellular to intracellular components. Aldosterone is released in response to hyperkalemia
Angiotensin	Directly enhances Na+ reabsorption in the proximal tubule, ascending limb, and collecting duct that incr Na+ transport
Antidiuretic Hormone (ADH, Vasopressin)	Released when animal is volume depleted, dehydrated, or hypotensive. Enhances Na+ reabsorptionin ascending limb and collecting duct
Endothelin	Produced in collecting duct and ascending limb where it acts to incr renal water and sodium excretion by inhibiting Na+K+ ATPase pump activity (shuts down pump). Decreased drive to pull Na+ in (stays in tubular fluid, gets excreted in urine)
Atrial Natruietic Peptide (ANP)	Produe in cardiac atria in response to atrial distention (indicator of vol). Enhances Na+ excretion in distal tubules and collecting duct by inhibiting aldosterone release and inhibiting ADH effects in collecting duct.
Parathyroid Hormone (PTH)	Acts on distal tubule to incr reabsorption of calcium
Calcitonin	Inhibits distal tubule reabsorption of calcium (allowing calcium to be excreted in urine)

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	Created by Shauna Ryner about 7 years ago