Week Five, Structure, Function, and Alterations Renal
Proteinuria
(1) Seen in certain kidney diseases, the negative charges on the basement membranes are lost even before there are noticeable changes in kidney histology, a condition referred to as minimal change nephropathy. (2) As a result of this loss of negative charges on the basement membranes: , the lower-molecular-wgt proteins, especially albumin, are filtered and appear in the urine.
Secondary active transport,
2 or more substances interact with a specific membrane protein (a carrier molecule) and are transported together across the membrane. As one substances diffuses down its electrochemical gradient, the energy released is used to drive another substance against its electrochemical gradient. The secondary active transport doesn't requires energy phosphate sources. Rather the direct source of the energy is that liberated by simultaneous facilitated diffusion of another transported substance down its own electrochemical gradient.
Manifestations of Kidney Stones
A colicky pain occurs as the rhythmic contractions of the ureter attempt to dislodge and advance the sharpedged stone. The accumulation of urine behind the stone causes infection or damage to organs. This consequence of obstruction depends on the location of the obstruction. If the obstruction is high and complete, glomerular filtration may be affected. The pain may be in the flankor between the last rib and the lumbar vertebrae, or it may radiate into the groin, depending on the stone's location. The pain may be accompanied by nausea and vomiting. Treatment involves dilution of stone-forming substances by a high fluid intake, extraction of larger stones by endoscopy, and fragmentation of stones by ultrasonic lithotripsy. Some smaller stones may pass spontaneously.
Pinocytosis-
Active transport mechanism for reabsorption of proteins, the process where the proteins attaches to the brush border of the luminal membrane, and this portion of the membrane then invaginates to the interiors of the cell until it's completely pinched off and a vesicle is formed containing the protein. Once inside the cell, the protein is digested into its constituent amino acids, which are reabsorbed through the basolateral membrane into the interstitial fluids. (Requires energy- active transport).
Increased Glomerular Capillary Colloid Osmotic Pressure decreases GFR:
As blood passes from the afferent arteriole through the glomerular capillaries to the efferent arterioles, the plasma protein concentration increases about 20%. The reason for this is that about ½ of the fluid in the capillaries filters into Bowman's capsule, thereby concentrating the glomerular plasma proteins that are not filtered. 2 factors that influence the glomerular capillary colloid osmotic pressure are 1) the arterial plasma colloid osmotic pressure and 2) the fraction of plasma filtered by the glomerular capillaries. Increasing the arterial plasma colloid osmotic pressure raises the glomerular capillary colloid osmotic pressure, which decreases GFR. Increasing the filtration fraction also concentrates the plasma proteins and raises the glomerular colloid osmotic pressure. With increasing renal blood flow, a lower fraction of the plasma is initially filtered out of the glomerular capillaries, causing a slower rise in the glomerular capillary colloid osmotic pressure and less inhibitory effect on GFR. A greater rate of blood flow into the glomerulus tends to increase GFR and a lower rate of blood flow into the glomerulus tends to decrease GFR.
Passive Water reabsorption
By way of osmosis is coupled mainly to sodium reabsorption When solutes are transported out of the tubule by either primary or secondary active transport, their concentrations tend to decrease inside the tubule while increasing in the renal intersitium. This creates a concentration difference that causes osmosis of water in the same direction that the solutes are transported, from the tubular lumen to the renal intersitium.
Renal Intersitial Hydrostatic and Colloid Osmotic Pressures
Changes in the peritubular capillary physical forces influence tubular reabsorption by changing the physical forces in the renal intersitium surrounding the tubules. When peritubular capillary reabsorption is reduced, there is increased interstitial fluid hydrostatic pressure and a tendency for greater amounts of solute and water to back leak into the tubular lumen, reducing the rate of net absorption. The opposite is true when there is increased peritubular capillary reabsorption above the normal level. An initial increase in reabsorption by the peritubular capillaries tends reduce interstitial fluid hydrostatic pressure and raise interstitial fluid colloid osmotic pressure. Both of these forces favor movement of fluid and solutes out if the tubular lumen and into the interstitium; therefore back leak of water and solutes into the tubular lumen is reduced and net tubular reabsorption increases. Forces that increase peritubular capillary reabsorption also increases reabsorption from the renal tubules. Conversely, hemodynamic changes that inhibit peritubular capillary reabsorption also inhibit tubular reabsorption of water and solutes.
Renal Failure Signs
Chronic kidney disease symptoms and signs do not develop until GFR and renal function decline to 25% of normal. The chronic alteration is primarily because of loss of nephron mass. The disease is associated with HTN, DM, or intrinsic kidney disease. Two factors advance the disease: Proteinuria → tubularinterstitial injury by accumulating in the interstitial space and activating mediators that promote progressive fibrosis Angiontensin II→ promotes glomerular HTN and hyperfiltration caused by efferent arteriolar vasoconstriction → systemic hypertension.
Afferent vs efferent constriction
Constriction of afferent arterioles reduces GFR. The effect of efferent arteriolar constriction depends on the severity of the constriction, modest efferent constriction raises GFR but severe efferent constriction reduces GFR.
What maintains GFR initially w/ AKI
During the early phases of hypoperfusion protective autoregulatory mechanisms maintain GFR at a relatively constant level through afferent arteriolar dilation and efferent arteriolar vasoconstriction (mediated by angiotensin II). Tubuloglomerular feedback mechanisms also maintain GFR and distal tubular nephron flow (see Chapter 37). The GFR ultimately declines because of the decrease in filtration pressure.
Describe the processes that impact the regulation of tubular reabsorption.
Glomerulotubular balance- the ability of the tubules to increase reabsorption rate in response to increased tubular load. The mechanism for controlling tubular reabsorption is the intrinsic ability of the tubules to increase their reabsorption rate in response to increased tubular load (increased tubular inflow). This phenomenon is referred to as glomerulotubular balance (GB). GB helps to prevent overloading of the distal tubular segments when GFR increases. Glomerulotubular balance acts as a second line of defense to buffer the effects of spontaneous changes in GFR on urine output. Regulation of peritubular capillary physical forces The 2 determinants of peritubuar capillary reabsorption that are directly influenced by renal hemodynamic changes are the hydrostatic and colloid osmotic pressures of the peritubular capillaries. The peritubular capillary hydrostatic pressure is influenced by the arterial pressure and resistance of the afferent and efferent arterioles. 1) Increases in arterial pressure tend to raise peritubular capillary hydrostatic pressure and decrease reabsorption rate. 2) Increase in resistance of either the afferent or the efferent arterioles reduces peritubular capillary hydrostatic pressure and tends to increase reabsorption rate. Colloid osmotic pressure of the plasma increases peritubular capillary reabsorption.
Peritubular Capillary and renal interstitial fluid physical forces:
Hydrostatic and colloid osmotic forces govern the rate of reabsorption across the peritubular capillaries. Changes in peritubular capillary reabsorption can influence the hydrostatic and colloid osmotic pressures of the renal interstitium and reabsorption of water and solutes from the renal tubules. The other factor that contributes to the high rate of fluid reabsorption in the peritubular capillaries is a large filtration coefficient (k1) b/c of the high hydraulic conductivity and large surface area of the capillaries.
Increased Glomerular Capillary Hydrostatic Pressure Increase GFR:
Increases in glomerular hydrostatic pressure raise GFR, whereas decreases in glomerular hydrostatic pressure reduce GFR. Glomerular hydrostatic pressure is determined by 3 variables 1) arterial pressure, 2) afferent arteriolar resistance and 3) efferent arteriolar resistance. Increased arterial pressure tends to raise glomerular hydrostatic pressure and increase GFR. Increased resistance of afferent arterioles reduces glomerular hydrostatic pressure and decreases GFR. Conversely dilation of the afferent arterioles increases both glomerular hydrostatic pressure and GFR. Constriction of afferent arterioles reduces GFR. The effect of efferent arteriolar constriction depends on the severity of the constriction, modest efferent constriction raises GFR but severe efferent constriction reduces GFR.
Increased Bowman 's capsule Hydrostatic pressure decreases GFR:
Increasing the hydrostatic pressure in Bowman's capsule reduces GFR whereas decreasing this pressure raises GFR. However, changes in Bowman's capsule pressure normally do not erve as a primary means for regulating GFR.
Describe the pathophysiology of renal calculi or kidney stones. Types (3) Study pages 742 and 743; refer to Figure 29-2
Kidney stones are caused by supersaturation of stone forming substances, change in urine pH, or urinary tract infections (UTIs). Calcium is a common constituent of renal stones; about 80% of stones, or renal calculi, are composed of calcium oxalate, calcium phosphate, or a combination of the two. Another stone, the struvite stone (which makes up 15% of stones), is composed of magnesium and ammonium phosphate. Uric acid stones (which accounts for about 7% of stones) may be seen with gout. Cystine stones are rare.
Transport Maximum Reabsorption
Most substances that are reabsorbed or secreted, there's a limit to the rate at which the solute can be transported often referred to as the transport maximum. This limit is due to saturation of the specific transport systems involved when the amount of solute delivered to the tubule exceeds the capacity of the carrier proteins and specific enzymes involved in the transport process.
Presentation AKI Intra
Oliguria is common (urine output less than 30 ml/hour) with intrarenal AKI, but anuria is rare. Creatinine values in septic renal injury may not reflect renal injury because sepsis decreases production of creatinine without major alterations in body weight, hematocrit level, or amount of extracellular fluid. Creatinine level usually increases with decreased renal blood flow and decreased GFR. However, in sepsis-induced AKI, creatinine values can remain within normal ranges.
Urinary Tract Obstruction Complications
Persistent partial obstruction impairs the ability to concentrate urine, reabsorb bicarbonate, excrete ammonia, and regulate metabolic acid-base balance. The body is able to partially counteract the negative consequences of unilateral obstruction by compensatory hypertrophy. This hypertrophy results from obligatory growth under the influence of growth hormone and compensatory growth under the influence of yet unidentified hormones. ***The contralateral, unobstructed kidney consequently increases the size of individual glomeruli and tubules, but not the total number of nephrons.**
PreRenal Acute Renal Injury Causes
Poor perfusion can result from renal artery thromobosis, hypotension related to hypovolemia (dehydration, diarrhea, fluid shifts) or hemorrhage, renal vasoconstriction and alterations in renal regional blood flow, microthrombi, or kidney edema that restricts arterial
Passive Diffusion Reabsorption
Reabsorption of Chloride, urea and other solutes. When Na is reabsorbed through the tubular epithelial cell, negative ions such as Cl are transported along with sodium b/c of electrical potentials. That is, transport of positively charged sodium ions out of the lumen leaves the inside of the lumen negatively charged compared with the interstitial fluid. This causes Cl ions to diffuse passively though the paracellular pathway. The active reabsorption of Na is closely coupled to the passive reabsorption of Cl by way of an electrical potential and a Cl concentration gradient. Cl ions can also be reabsorbed by secondary active transport. The most imp secondary active transport processes for Cl reabsorption involves co- transport of Cl with Na across the luminal membrane. Urea concentration in the tubular lumen increases, causing concentration gradient favoring the reabsorption of urea.
What determines GFR
The GFR is determined by 1) the sum of the hydrostatic and colloid osmotic forces across the glomerular membrane, which gives the net filtration pressure and 2) the glomerular capillary filtration (k1). The net filtration pressure represents the sum of the hydrostatic and colloid osmotic forces that either favor or oppose filtration across the glomerular capillaries.
Diagnosis of Pre / Intr / Post Acute Renal Injury
The diagnosis and degree of renal injury can be described by the acronym RIFLE. R = risk (GFR decreases 25%), I = injury (GFR decreases 50%), F =failure (GFR decreases 75%), L = loss, and E = end-stage kidney disease.
Functions of Kidneys
The function of the nephron is to form a filtrate of protein- free plasma. This process, known as ultrafiltration, occurs across the glomerular membrane. The nephron then regulates the filtrate to maintain body fluid volume, electrolyte composition and pH within narrow limits. Glomerulus filtration, tubular reabsorption, and tubular secretion. Summary: The 3 processes by which the kidneys excrete urine. Water, electrolytes, glucose and organs molecules are filtered at the glomerulus. Sodium and glucose are reabsorbed into peritubular capillaries by active transport from the proximal convoluted tubules and water reabsorption follows by osmosis. Sodium is reabsorbed by active transport from distal convoluted tubule, more sodium is conserved when aldosterone is secreted. Osmotic reabsorption of water form them occurs when ADH is present. Secretion of ammonia, hydrogen, and potassium occurs form peritubular capillaries into distal tubules by active transport.
loops of Henle
The hairpin- selectively transport solutes and water, contributing to the hypertonic state of the medulla.
Increased Glomerular Capillary Filtration:
The k1 is a measure of the product of the hydraulic conductivity and surface area of the glomerular capillaries. K1= GFR/ net filtration pressure Although increased K1 raises GFR and decreased k1 reduces GFR, changes in K1 do not provide a primary mechanism for the normal day to day regulation of GFR.
Function of Kidneys
The major function of the kidney is urine formation and involves the processes of filtration, reabsorption and secretion. These processes are the function of the nephrons. Fluid is filtered at the glomerulus. Substances are reabsorbed from the filtrate or secreted into the filtrate by the renal tubules. The final urine flows into the minor and major calyces, and then is propelled by the ureters to the bladder for storage and elimination.
Glomerulotubular balance
The mechanism for controlling tubular reabsorption is the intrinsic ability of the tubules to increase their reabsorption rate in response to increased tubular load (increased tubular inflow).
Common Pathogens UTI
The most common route in the development of acute UTI is by an ascending infection and are complicated by abnormalities in the urinary tract. Common pathogens in these infections are the gram-negative rods, namely Escherichia coli, Klebsiella, Staphylococcus saprophyticus, Proteus, and Pseudomonas. Other possible infectious agents are gram-positive cocci, tubercular bacilli, and fungi.
Progression of injury and recovery acute renal injury (3)
The progression of injury with recovery of renal function occurs in three phases:(1) initiation, (2) maintenance, and (3) recovery. The initiation phase is reduced profusion or toxicity in which injury is evolving. The maintenance phase is the period of established injury and dysfunction after the initial event has been resolved. It can last from weeks to months. During the recovery phase, the injury is repaired and normal function is reestablished. Diuresis is common in this phase and is accompanied by a decline in serum creatinine and urea concentrations and an increase in creatinine clearance.
Regulation of the filtrate occurs through 2 processes; tubular reabsorption and tubular secretion.
Tubular reabsorption is the movement of fluids and solutes from the tubular from the tubular lumen to the peritubular capillary plasma. Transfer of substances from the plasma of the peritubular capillary to the tubular lumen is tubular secretion.
The distal tubule
adjusts acid- base balance by excreting acid into the urine and forming new bicarbonate ions.
Acute tubular necrosis (ATN)
caused by ischemia is the most common cause of intrarenal AKI. It occurs most often after surgery (40% to 50% of cases) but is also associated with severe sepsis; obstetric complications; and severe trauma, including severe burns; or small vessel vasculitis. A combination of events and predisposing factors leads to the greatest risk for acute renal failure.
outer cortex
containing the glomeruli and an inner medulla containing the tubules and collecting ducts that drain into the calyces.
The glomerulus
contains loops of capillaries that loop in the Bowman capsule. The capillary walls serve a s a filtration membrane for the formation of the primary urine. The layers of the glomerular capillary include the endothelium, basement membrane and epithelium. The epithlium is composed of podocytes that interlock to provide filtration slits.
The colleting duct
contains principal cells that resorb Na and H2O and excrete potassium and intercalated cells that secrete hydrogen or bicarbonate and potassium.
upper urinary tract obstruction.
defined as blockage of urine flow within the urinary tract. obstructive uropathy is any anatomic or functional blockage that leads to urinary stasis, dilates the urinary system, increases the risk of infection, and generally compromises function.Complete obstruction of the upper urinary tract causes dilation of the ureter (hydroureter) and of the renal pelvis and calyces (hydronephrosis). Within days, tubulointerstitial fibrosis and apoptosis develop, and if these conditions are not relieved, irreversible renal damage occurs. Persistent partial obstruction impairs the ability to concentrate urine, reabsorb bicarbonate, excrete ammonia, and regulate metabolic acid-base balance. The body is able to partially counteract the negative consequences of unilateral obstruction by compensatory hypertrophy. This hypertrophy results from obligatory growth under the influence of growth hormone and compensatory growth under the influence of yet unidentified hormones. The contralateral, unobstructed kidney consequently increases the size of individual glomeruli and tubules, but not the total number of nephrons.
The ureters
extend from the renal pelvis to the posterior wall of the bladder. Urine flows through the ureters by means of peristaltic contraction of the ureteral muscles.
Azotemia
increased serum urea levels and frequently increased creatinine levels as well. Renal insufficiency or renal failure causes azotemia. Both azotemia and uremia indicate an accumulation of nitrogenous waste products in the blood, a common characteristic that explains the overlap in definitions of terms.
The bladder
is a bag composed of the detrusor and trigone muscles and innervated by parasympathetic fibers. When accumulation of urine reaches 250-300ml, mechanoreceptors, which respond to stretching of tissue, stimulate the micturition refelex.
Overactive bladder (OAB)
is an uncontrollable or premature contraction resulting in urgency with or without incontinence, frequency, and nocturia.
Detrusor sphincter dyssynergia
is failure of the urethrovesical junction smooth muscle to release urine during micturition and causes a functional obstruction.
The proximal tubule
is lined with microvilli to increase surface area and enhance reabsorption,
PreRenal Acute Renal Injury
is the most common cause of AKI. Reduced effective arterial blood volume causes renal hypoperfusion that occurs rapidly over a period of hours with elevation of BUN and plasma creatinine levels. During the early phases of hypoperfusion protective autoregulatory mechanisms maintain GFR at a relatively constant level through afferent arteriolar dilation and efferent arteriolar vasoconstriction (mediated by angiotensin II). Tubuloglomerular feedback mechanisms also maintain GFR and distal tubular nephron flow (see Chapter 37). The GFR ultimately declines because of the decrease in filtration pressure.
The Bowman capsule
is the space between the visceral and parietal epithelium.
The nephron
is the urine-forming unit of the kidney and is composed of the glomerulus, proximal tubule, hairpin loos of Henle, distal tubule and collecting duct.
The calyces
join to form the renal pelvis and are continuous with the upper end of the ureter.
Mesangial cells and matrix
lie between and support the glomerular capillaries in the Bowman capsule.
Intrarenal (intrinsic) acute kidney injury (AKI)
may result from ischemic acute tubular necrosis (ATN), nephrotoxic ATN (i.e., exposure to radiocontrast media or antibiotics), acute glomerulonephritis, vascular disease (malignant hypertension, disseminated intravascular coagulation, and renal vasculitis), allograft rejection, or interstitial disease (drug allergy, infection, tumor growth). The terms acute tubular necrosis and acute kidney injury are sometimes used interchangeably, but the conditions are not the same because acute kidney injury can occur without ATN. ATN is generally described as postischemic or nephrotoxic or it can be a combination of both. Postischemic ATN involves persistent hypotension, hypoperfusion, and hypoxemia, producing ischemia and reduced levels of ATP and generating toxic oxygen-free radicals with loss of antioxidant protection that causes cell swelling, injury, and necrosis. Activation of inflammatory cells (e.g., neutrophils, macrophages, and lymphocytes) and complement and release of inflammatory cytokines contribute to tubular injury. Transport of sodium and other molecules is disrupted with damage primarily to the proximal tubular epithelium and shedding of the brush border with the appearance of tubular granular casts in the urine. Ischemic necrosis tends to be patchy and may be distributed along any part of the nephron tubules. Injury is most severe in the outer medulla with scattered necrosis in the cortex and loss of cells along the tubular epithelium.140 Severe disease of the glomeruli (i.e., acute or rapidly progressive glomerulonephritis) or renal microvascular disorders can also cause intrinsic kidney injury. Nephrotoxic ATN can be produced by numerous antibiotics, but the aminoglycosides (gentamicin, tobramycin) are the major culprits. The drugs tend to accumulate in the renal cortex and may not cause renal failure until after treatment is complete. Radiocontrast media (x-ray media) and cisplatin also may be nephrotoxic. Dehydration, advanced age, concurrent renal insufficiency, and diabetes mellitus tend to enhance nephrotoxicity from either aminoglycosides or radiocontrast media. Other substances such as carbon tetrachloride, heavy metals (mercury, arsenic), methoxyflurane anesthesia, or bacterial toxins may promote renal failure. Endogenous substances toxic to renal tubules are excessive myoglobin (oxygen-transporting substance in muscles) and hemoglobin.
Neurogenic Bladder (3)
neurogenic bladder is a functional lower urinary tract obstruction caused by an interruption of the nerve supply to the bladder. Upper motor neuron lesions result in hyperreflexive bladder and uncoordinated contractions. Lower motor neuron lesions result in underactive, hypotonic, or atonic bladder function. Detrusor / UAB / OAB Because of disordered neural sensation, symptoms are difficult to assess. Management involves catheterization, drugs, or surgery to relieve obstruction. Any infection must be treated with appropriate antibiotics.
Uremia
numerous consequences related to renal failure, including retention of toxic wastes, deficiency states, electrolyte disorders, and immune activation promoting a proinflammatory state.
Underactive bladder (UAB)
occurs when the duration or strength of contraction is inadequate to empty the bladder and results in distention and incontinence.
Postrenal acute kidney injury
rare and usually occurs with urinary tract obstruction that affects the kidneys bilaterally (e.g., bilateral ureteral obstruction, bladder outlet obstruction-prostatic hypertrophy, tumors or neurogenic bladder, and urethral obstruction). The obstruction causes an increase in intraluminal pressure upstream from the site of obstruction with a gradual decrease in GFR. A pattern of several hours of anuria with flank pain followed by polyuria is a characteristic finding. This type of AKI can occur after diagnostic catheterization of the ureters, a procedure that may cause edema with obstruction of the tubular lumen.
Juxtaglomerular cells
secrete renin and are located around the afferent arteriole. They are contiguous with the sodium-sensing macula densa cells for the distal convoluted tubule.
Acute Renal Injury Manifestations:
three phases: initiation phase, maintenance phase, and recovery phase. (1) The initiation phase is the phase of reduced perfusion or toxicity in which renal injury is evolving, usually lasting 24 to 36 hours. Prevention of injury is possible during this phase. (2)The maintenance or oliguric phase is the period of established renal injury and dysfunction after the initiating event has been resolved and may last from weeks to months. Urine output is lowest during this phase, and serum creatinine, blood urea nitrogen, and serum potassium levels increase; metabolic acidosis develops; and there is salt and water overload. (3) The recovery phase is the interval when renal injury is repaired and normal renal function is reestablished. GFR returns toward normal but the regenerating tubules cannot concentrate the filtrate. Diuresis is common during this phase, with a decline in serum creatinine and urea levels and an increase in creatinine clearance. Polyuria can result in excessive loss of sodium, potassium, and water. Fluid and electrolyte balance requires careful maintenance.
