RenalObjectives.docx

**RENAL STUDY GUIDE** **RENAL AND URINARY TRACT ANATOMY** ***Functions of the Kidney: Homeostasis, Endocrine, and Metabolic*** - - - - - - - - ***Renal Vasculature*** - - - - - - - - ***Blood Flow Through the Kidney*** - Capillaries in the kidneys go from a...

**RENAL STUDY GUIDE** **RENAL AND URINARY TRACT ANATOMY** ***Functions of the Kidney: Homeostasis, Endocrine, and Metabolic*** - - - - - - - - ***Renal Vasculature*** - - - - - - - - ***Blood Flow Through the Kidney*** - Capillaries in the kidneys go from artery artery - 30% of the population has more than 1 artery supplying a kidney - Segmental arteries do not have collateral vessels - Long term overactivity of the SNS can lead to decreased kidney function as well as cardiac hypertrophy ***Urologic System Functions*** - ***Flow Through the Kidney:*** - - ***Renal Anatomy: 2 kidneys, 2 ureters, 1 bladder (detrusor and trigone muscles), 1 urethra (3-4 cm in women; 18-20 cm in men)*** - - - - - - - - - **Parasympathetic innervation of bladder and internal urethral sphincters**. -- Allows you to voluntarily void - SNS innervates bladder neck, vas deferens, seminal vesicles, prostate. - Skeletal muscle motor neurons in external urethral sphincter. Pudendal nerve. **Nephron:** Functional unit of the kidney. Each kidney contains 1 million nephrons. - - - ***Nephron Contains:*** **In Renal Cortex:** - - - - **[Mesangial Cells ]** - Contractile cells with macrophage like properties/immune defense/repair of glomerulus - Regulate capillary flow and surface area available to form ultrafiltrate - Clear the endothelial cells and podocytes of protein - **[Bowman's Capsule]** - Epithelial cup surrounding capillaries where filtrate collects to go onto tubules - - **Function: bulk reabsorption of solutes and water into blood** - **Sodium (65%) is actively transported from the proximal tubule and into the peritubular interstitial; consumes a large quantity of oxygen** - Potassium, chloride, and bicarbonate follow sodium in direct proportion by the sodium co-transport mechanism -- 65% of these ions are also reabsorbed here - Water (65%) follows sodium by osmosis/passive diffusion ("where sodium goes, water goes") - **Reabsorption of water leaves an increased concentration of urea** - **Glomerulotubualr balance - Reabsorption of sodium and water is proportional in the PCT** - **When the GFR spontaneously decreases or increases, the renal tubules (primarily the proximal tubules) automatically adjust their rate of reabsorption of sodium and water to balance the change in GFR** - Solute secretion, hormone production, gluconeogenesis - - **Function**: establish a hyperosmotic state with the medullary interstitial fluid; participate in forming concentrated or dilute urine. **The Loop of Henle separates the handling of water and sodium.** - **The ability of the kidneys to produce concentrated or dilute urine depends on the presence of a graduated hyperosmotic peritubular interstitium. Must be an osmotic gradient across the renal medulla to produce variable urine concentration.** - **Two countercurrent systems are needed to create and maintain the graduated hyperosmotic peritubular interstitum:** - **Loop of Henle -- countercurrent multiplier system that creates the osmotic gradient** - **Vasa recta -- countercurrent exchanger system that maintains the medullary osmotic gradient** - **Returns the reabsorbed water to the blood, allowing the osmolarity in the interstitum to remain high** - Without this, we would produce dilute urine, leading to dehydration - **Thin, descending segment** -- highly permeable to water and moderately permeable to sodium, urea, and other solutes (less mitochondria/microvilli) - **20% of water is reabsorbed here (back to peritubular capillaries)** - **Concentrates NaCl in the tubular fluid, which is delivered to the thick ascending limb** - Hyperosmotic fluid causes water to leave the descending limb; the remaining ultrafiltrate (fluid) becomes increasingly concentrated - The osmolarity of the peritubular interstitum progressively increases as the descending limb travels from the cortex to the medulla (300-1500 in the renal pelvis). The increasing osmolarity provides the energy for passively reabsorbing water (osmosis). - **Thin, ascending segment** -- more permeable to solutes and almost impermeable to water (more microvilli/mitochondria to transport sodium actively and dilute the urine) -- pumps out salt - **Thick, ascending segment** -- highly permeable to sodium, potassium, and chloride and significantly less permeable to water and urea (more microvilli/mitochondria to transport sodium actively and dilute the urine) - Uses active transport to move chloride and sodium into the medullary interstitum - Water cannot follow sodium into the peritubular interstitum so the tubular fluid becomes dilute and the peritubular interstitium becomes concentrated. - **Thick ascending limb pumps out sodium -- makes the environment super salty, so when new filtrate enters through the descending limb water will passively leave due to the salty interstitial space/renal medulla -- saltiness does not get diluted with water because it is reabsorbed by blood (why we aren't dehydrated!)** - Fluid leaving the ascending limb of the loop is hypoosmotic and is more diluted than the fluid that entered - Ultrafiltrate/fluid becomes more and more dilute as it encounters the distal tubule - - Sodium is reabsorbed, and potassium, chloride and bicarbonate follow - **The late distal tubule is almost impermeable to water except in the presence of aldosterone (Na and water) or ADH (just water);** these hormones can fine tune the final urine concentration - - Performs final adjustments in urine composition (work on solutes, not water -- limited permeability) - K, Na is absorbed by distal tubule and collecting duct due to aldosterone - **Straight segment of the distal tubule and the collecting duct is permeable to water as controlled by ADH or aldosterone** - **ANP inhibits water and sodium reabsorption** - Tamm-Horsfall glycoprotein (uromodulin) -- protective mechanism - Most abundant urinary protein - Protects against bacterial adhesion and urolithiasis (kidney stones) - Renal ligand for lymphokines - Damage to distal convoluted tubules/collecting duct, increased risk of infection - - - **Urine Formation/Nephron functions:** **1. Glomerular filtration**, **2. Tubular Reabsorption**, **3. Tubular Secretion 4. Excretion** - Renal blood flow is one factor that affects GFR, **RBF DOES NOT** equal Pressure - RBF originates at kidney's hilum - Kidneys receive 1000-2000 mL of blood per minute - GFR -- filtration of plasma into Bowman space - 20% of RBF (120-140 mL/min) becomes filtrate - Directly r/t to the perfusion pressure in the glomerular capillaries - Renal Plasma Flow = RBF minus RBCs (and other blood cells) - Amount of blood volume that reaches the glomerulus - Not all of that 1L blood/min is filtered -- blood cells are not - In normal kidneys, RBF \~635 mL/min - - **Amount of fluid that flows into Bowman's capsule per unit of time** - **Normal: 90-120 mL/min** - **20% of renal blood flow is filtered by the glomerulus, 80% is delivered to the peritubular capillaries (water, electrolytes, and glucose are freely filtered. Plasma proteins are not).** - - - - - - **Filterability of substances is determined by:** - - ***Why do glomerular capillaries have higher filtration rates?*** ↑ Hydrostatic Pressure, ↑ Capillary filtration coefficient  ***Starling Forces & GFR*** - - - **Capillary Hydrostatic pressure drops as blood travels through the capillary bed into the venules and veins** - **Capsular hydrostatic pressure -- pressure the fluid in the glomerular capsule exerts against the filtration membrane** - - - *Decreasing the efferent arteriolar resistance increases the RBF through the glomerulus, but it decreases the hydrostatic pressure in the glomerulus, thus GFR decreases* - *Vasoconstriction leads to increased resistance* **Forces Favoring Filtration:** - - **3 DETERMINANTS -- ARTERIAL BP, AFFERENT PRESSURE, AND EFFERENT PRESSURE** - **Forces Opposing Filtration:** - - -  The net filtration pressure is the driving force that pushes fluid from the blood (glomerulus) into Bowman's capsule. **To calculate GFR:** - - - - - - - - - - *2 Mechanisms of Autoregulation:* - - **Without autoregulation, when MAP decreases or vascular resistance increases, then the RBF would decrease!** - **When renal perfusion is too low, autoregulation increases renal blood flow by reducing renal vascular resistance** - **When renal perfusion is too high, autoregulation decreases renal blood flow by increasing renal vascular resistance** - Balances pressure between afferent and efferent arterioles - **When renal perfusion is 80-180, there is a constant RBF and GFR** - **Sustaining renal perfusion via autoregulation translates to a systemic MAP \~/\> 65-80 (highly dependent on DBP)** - Prevents wide fluctuations in systemic arterial pressure from transmitting to glomerular capillaries - Ex: As the systemic BP increases, afferent arterioles constrict, preventing an increase in filtration/hydrostatic pressure 1. **Myogenic:** immediate. impact of arterial pressure on renal arterioles. - - 2. **Tubuloglomerular Feedback:** delayed (seconds to minutes later). Macula densa feedback. - - - **Neural Regulation:** - - **No parasympathetic effects!** - - - **Hormone Regulation: Affect RBF and GFR!** - - - - - V2 receptors on collecting ducts. - Controls final concentration of urine - Regulates aquaporin expression - - Inhibit Na & H~2~O reabsorption by kidney tubules. Inhibit secretion of Renin & Aldosterone. Vasodilate afferent arterioles & constrict efferent arterioles → to ↑ urine formation and ↓ blood volume & BP. ↑ water loss - A type -- myocardial cells in atria - B type -- secreted from myocardial cells in the ventricles - - - - **Activated alpha 1 receptors promote afferent arteriole vasoconstriction, decreasing GFR and RBF** - **Increases sodium reabsorption in proximal tubule** - - - - ***In ↓ Renal Perfusion:*** (Myogenic autoregulation & Vasodilatory PGE → Afferent vasodilation) & (↑ Angiotensin II → Efferent Vasoconstriction) = **MAINTENANCE OF GFR.** **Urine Formation** (**Tubular reabsorption** & **Tubular Secretion**) -- tubular transport back into the plasma - - **Approx. 60 -- 70% of filtered sodium and water and approx. 50% of urea are reabsorbed, along with 90% or more of potassium, glucose, bicarbonate, calcium, phosphate, amino acids, and uric acid.** - **Active Transport** - **Can become limited as carrier molecules become saturated** - **Facilitated Transport** - **Used to move filtrate solutes like glucose into interstitial fluid and peritubular capillaries** - **Passive diffusion is used to reabsorb chloride, water and urea** - **Damaged renal tubules -- metabolic byproducts and drugs may accumulate, causing toxicity** - **[Proximal Convoluted Tubules]** - **[Loop of Henle ]** - **[Distal Convoluted tubules and collecting duct ]** - **[Mechanisms of Urine Concentration and Dilution]** - Urea (end product of protein metabolism and major constituent of urine) - Formed by liver from ammonia - Filtered into the renal capsule, limited reabsorption in tubules - Urea is moved from filtrate into the interstitum at the medullary tubules (via facilitated diffusion), creating a concentration gradient pulls water into interstitum - This pull concentrates urine - Urea is then secreted in the thin ascending limb - Under the influence of ADH, urea moves back into the interstitum at the distal tubule - 50% of urea is excreted in the urine 50% is retained in interstitial fluid in kidneys - Countercurrent multiplier/Exchange -- **look up video on this...** - **Occurs in extra long Loops of Henle** - An osmotic gradient in the medullary interstitial fluid is created - Produces concentrated urine - The longer the loop, the greater the concentration gradient/concentration ability - - **Can be unidirectional or bidirectional** - **Ex: secretion from peritubular capillaries through interstitial fluid, then back through tubular epithelial cells** - **Secreted substances include: urea, creatinine, caffeine. Many antibiotics, potassium, acids, and bases.** - **4. Tubular Excretion**: the result of filtration, absorption, and secretion processes - Urine is the product - Transfer of solutes (that are too large to be filtered by the glomerulus or are in excess in the blood) form the peritubular capillaries to the renal tubular lumen → urinary excretion (active transport) - The process by which metabolites, molecules, drugs and the like are IRREVERSIBLY transferred from the internal to the external environment - Factors that alter excretion: urine pH, binding to proteins, diseases states, negative, changes in GFR **Renal Function Tests** - - Best way to estimate the functioning of renal tissue (normal = 120/min) - **Directly measured by the clearance of exogenous filtration markers** - Requires 24 hour urine collection + 1 blood sample; multiple blood collections; nuclear renal scan - Accurate and expensive - **Estimated/calculated indirectly by endogenous markers (serum creatinine and cystatin C**) - Widely used, acceptable and cheap - Inaccurate and imprecise unless GFR \20 and oliguric [ ]**-- consider renal injury, ATN - **\>20 and hyponatremic** -- consider renal salt wasting, cerebral salt wasting, SIADH, adrenal insufficiency, diuretic use - - Plasma protein is freely filtered at the glomerulus - Measures progressive renal dysfunction - **Urinalysis Tests Kidney Function** - **Urine color/clarity** - **Urine pH** (5-6.5) - **Specific gravity** (1.016-1.022) - **Urine osmolality (300-900 mOsm/kg)** - More accurate than specific gravity in the presence of urea and glucose - High in pre-renal AKI - **Urine sediment** - **Reagent strips** - **Leukoesterase (negative) --** enzyme in WBCs, indicates infection - **Nitrates (negative) --** byproduct of bacterial metabolism, indicates infection - If you have hematuria (one time), repeat test - Avoid ordering follow up urine cultures after treatment of uncomplicated UTI in patients that show clinical resolution of infection - **[Quiz Questions:]** 1\. When a cell shrinks after being placed in an aqueous solution, the solution is most likely hypotonic. **False** 2\. When the juxtamedullary nephrons are all non-functional, a person's risk for dehydration increases. **True** 3\. Increased blood volume will inhibit proximal tubule reabsorption. **True (When BP or blood volume is increased, the kidneys reduce sodium and water reabsorption in the proximal tubules to return blood pressures and fluid volume to normal)** 4\. ADH acts to concentrate urine by stimulating the reabsorption of sodium chloride and water in the proximal tubule. **False** 5\. The countercurrent exchange in the kidney is associated with shorter loops of Henle. **False** 6\. If a person's glomerular filtration membrane has been injured, which structures would be affected? **Podocytes** 7\. One of the forces favoring filtration in the glomerulus is: **capillary hydrostatic pressure** 8\. The primary function of the Loop of Henle is to: **establish a hyperosmotic state within the medullary interstitial fluid.**. **General Kidney Fluid and Electrolyte Balance** - **Basic Concepts** - **Tonicity -- iso, hypo, hyper** - **Osmolarity -- mOsm/L** - **Concentration gradients -- result from unequal distribution of water or solute across a semipermeable membrane** - **Total body water- 60% of body weight** - **ICF 40% body weight; ECF 20% of body weight** - **ICF and ECF are separated by a semipermeable membrane** - **Non-penetrating solutes (ions) need assistance** - **Sodium** - **Hypernatremia can result from net gain of salt or net loss of water** - **Hyponatremia can result from net loss of salt or net gain of water (alcoholics, SSRIs)** - **Pseudohyponatremia can occur from hyperglycemia, hyperlipidemia, high serum proteins, hyperuremia** - **Potassium** - **Hyperkalemia:** - **Increased intake** - **Decreased urinary excretion (hypoaldosteronism, kidney failure)** - **Intracellular extracellular shifts (acidosis, trauma/cell destruction, beta blockers, low insulin)** - **Low catecholamines** - **Low flow to distal nephron** - **Hypokalemia:** - **Decreased intake** - **Increased urinary excretion (renal/diuretics or GI loss)** - **Loop and Thiazide diuretics** - **Extracellular intracellular shift (alkalosis, beta agonists, hyperinsulinemia)** - **Chloride** - **Hyperchloremia \>122** - **Hypothesized to cause renal hypoperfusion and AKI due to renal vascular smooth muscle constrictor effect** - **Hypochloremia** **Embryonic Development** - **Kidneys develop from:** - **Pronephros -- connects primitive wolffian duct to cloaca as the foundation for male sexual development** - **Mesonephros -- nonfunctional** - **Metanephros -- ureteric bud, metanephrogenic mesenchyme, functional kidney** - **Urine formation and excretion begin by the third month of gestation** **Age and Renal Function** - - - - - - - - - - - - - - - - - Why older adults are at increased risk of AKI/CKD -- already reduced GFR  **Urinary Obstruction:** blockage of urine within the urinary tract. - - - - - Severity is based on location (kidney, ureter, bladder, urethra), degree of obstruction, rapidity of occurrence, unilateral vs bilateral, acute v chronic, etiology (calculi, carcinoma, papilla, infection, trauma, clots, ectopy, fibrosis) - - **Common problem** - **Children more than adults** - **Men more than women** - - **Neurogenic Bladder** - Bladder dysfunction caused by neurologic disorders; problems with urine storage or voiding - **Upper motor neurons** - **Dyssynergia** -- overactive/hyper reflexive bladder function - **Detrustor hyperreflexia --** the bladder muscle contracts to often and involuntarily - **Detrusor hyperreflexia with detrusor dyssynergia** -- both the bladder and sphincter are contracting at the same time, causing a functional obstruction of the bladder outlet - **Lower motor neurons** - **Detrusor areflexia** -- underactive, hypotonic, atonic bladder - **Clinical Manifestations:** - Frequent daytime voiding -- more often than every 2 hours while awake - Nocturia -- night time voiding - Urgency with hesitancy - Dysuria - Intermittency of urinary stream - Feelings of incomplete bladder emptying, despite micturition - **Knowledge Check: A person has a lesion on the lower neuron that involves the sacral micturition center. Which condition is the person experiencing?** Detrusor areflexia - **Hypospadias** - Urethral meatus is located on the ventral side or underside of the penis - Tx: Surgery - **Epispadias** - Males: urethral opening is on the dorsal/top surface of the penis - Females: cleft along the ventral urethra usually extends to the bladder neck - Twice as many boys are affected as girls - Tx: surgery may be needed - **Bladder outlet obstruct** - Urethral valves -- thin membranes that occlude the urethral lumen and obstructs urinary outflow in male infants - Tx: prenatal bladder shunting; with resection during the first days of life - **Exstrophy of the bladder** - Pubic bones are separated and the lower abdominal wall and anterior wall of bladder is missing - **Renal aplasia/agenesis** - **Agenesis -- kidney did not grow. Aplasia -- is the billing code?** - Absence of one or both kidneys - Potter syndrome (bilateral renal agenesis) -- incompatible with extrauterine life - **Hypoplastic kidneys** - Small with a decreased number of nephrons - **Renal dysplasia** - Results from abnormal differentiation of renal tissues (primitive glomeruli and tubules, and non-renal tissue may occur) - **Polycystic kidney disease** - Autosomal dominant mutation of PKD-1 (chromosome 16) and PKD-2 (chromosome 4) - Cyst formation and obstruction, accompanied by the destruction of renal parenchyma, interstitial fibrosis, and loss of functional neurons - Leads to kidney failure - Volume of cysts will decrease perfusion - **Kidney stones** - **Patho:** - 80% calcium oxalate, can be combos of others - Soluble material supersaturates urine; initial formation in kidney medullary interstitum - **Risks:** - Male, inadequate fluid intake, geographic location, temperature - Increased fluid and calcium (if oxalate) intake may reduce risk - **Clinical Manifestations** - Asymptomatic -- up to 70% - Patients reports pain/renal colic - Hematuria - **Tx:** - Manage pain - Promote stone passage - Expulsive drugs -- alpha blocker (tamsulosin), CCB (nifedipine), antispasmodic agents - Urologic consult -- remove stones using percutaneous nephrolithotomy, ureteroscopy, laser lithotripsy - reduce the concentration of stone forming substances - adjust pH of urine - increased fluid and calcium intake may reduce risk. - - Pain (bladder distension, secondary to infection, obstructing stone or masses) - Changes/decrease in UOP - Hypertension if retained Na+ and water - Reports hematuria, pyuria - Distended lower abdomen (hematuria, pyuria) - Early diagnosis to prevent kidney injury - *Beware of post obstructive diuresis caused by relief of obstruction -- may cause fluid and electrolyte imbalance* **Knowledge Check:** Name 3 anatomic alterations that contribute to Urinary Incontinence. **Obesity, pregnancy, BPH, weak pelvic floor?** A child with unilateral renal agenesis is seen in the clinic. The nurse realizes the child a\. requires dialysis. **b. has a hypertrophied kidney (one remaining kidney overgrew)**. c. may have facial anomalies. d. is more susceptible to infections. **Urinary Incontinence:** involuntary leakage of urine - **Etiology:** - Brain disease (stroke, Parkinson's, trauma) - Associated risk with greater age, obesity, parity, family hx - High impact activities, smoking, caffeine intake - More common in women - **Patho: 4 types** - **Stress** -- weakened/damaged urethral sphincter, weakened/damaged pelvic floor muscles - **Urge** (overactive bladder) -- physical injury, neurologic disease, diabetes, infection - **Overflow** -- obstruction (BPH, kidney stones, tumor) - **Functional** -- physical/mental disability that impairs mobility/ability to reach the bathroom (dementia, diuretics) - **Clinical Presentation:** - Rapid, strong urge to urinate, little or no urge to urinate, or inability - Mild/small volume to total loss of bladder control - Aggravating factors -- sneezing, coughing, laughing, UTI, meds, pregnancy, obesity - Alleviating factors -- avoid exercise/activity, stop meds - **Pediatric Incontinence** - Enuresis: at least 2x month after 6 - May be due to stress/behavior problems, family hx, boys more common - Tx: education, behavioral (timed voiding, fluid management), meds: anticholinergic or alpha-blocker (daytime), desmopressin (night) **Renal Tumors** - Renal adenomas: benign - Renal cell carcinoma: most common - **Clinical sx:** - Hematuria -- all renal tumors are highly associated with hematuria. - Dull and aching flank pain - Palpable mass in thinner individuals - **Wilms Tumor (Nephroblastoma)** -- arises from mutations of Wilms tumor-suppressors genes - Embryonal tumor of the kidney - Most common solid tumor of children, usually dx between 1-5 years of age - Arises from proliferation of abnormal renal stem cells - Manifestations: - Enlarging upper abdominal mass in a healthy, thriving child - Vague abdominal pain, hematuria, fever, and htn - **Bladder tumors** - **Risks:** smoking, chronic cystitis - **Clinical Sx:** - Hematuria - Irritative voiding s/s - Flank/suprapubic pain - Fatigue - Weight loss **Urinary Tract Infection (UTI):** Infection of the urinary epithelium caused by bacterial infection (urethra, bladder (cystitis), ureters/renal pelvis/interstitium (pyelonephritis)). - - Upper/lower -- pyelonephritis vs bladder - Severity---sx that suggest infection beyond the bladder such as fever, chills/rigor, - - Cystitis E. coli - Urethritis (chlamydia, herpes) - Vaginitis - - Frequency, urgency, dysuria, fever - Suprapubic tenderness or pain - Pelvic exam for vaginitis - - - Uncomplicated -- 3 days of antimicrobial - Young women - Complicated -- a minimum of 7 days abx - Pregnant women, men, children **Knowledge Check** 4\. Mechanisms that protect the urinary tract from infection include a. monocytes in the urine. **b. acidic urine.** c. decreased urine osmolarity. d. type-I pili. 5\. A child has a UTI. Which assessment finding is most typical in this condition? e. Enlarging asymptomatic upper abdominal mass f. Periorbital edema that descends into the extremities g. Prodromal gastrointestinal illness with diarrhea h. **Incontinence in a previously dry child** **Acute Cystitis:** **painful bladder syndrome or interstitial cystitis is not an infection** - - **Protects the epithelial cells by preventing acids and toxins from encountering this layer** - Disrupted in painful bladder syndrome - Can occur from recurrent UTIs - - **Pyelonephritis -- infection of the upper urinary tract** - - - - -  - - **Complications:** kidney scarring (substitute fibrotic tissue for functional tissue), HTN, renal failure - **Clinical Sx:** often asymptomatic (esp. in children), UTI s/s - **Tx:** prolonged abx with recurrent infection - **Vesicoureteral Reflex** - **Retrograde urine flow from bladder into ureters or kidneys** - **Encourages infected urine from bladder to be swept up into kidneys causing frequent pyelonephritis** - **Patho: caused by a congenital abnormality or ectopic insertion of the ureter into the bladder** - **Clinical Sx:** - **Asymptomatic** - **Recurrent UTIs, unexplained fever, poor growth and development, feeding problems** - **Family hx may reveal UTIs** **Glomerulonephritis:** Inflammation of the glomeruli - - **Adults -- uncommon, associated with immunocompromised, older age** - **Children -- pharyngitis, impetigo** - **Patho:** - **Noninfectious** - **Infectious: antibodies produced against an organism react with the glomerular endothelial cells** - **Activation of complement, recruitment and activation of immune cells and mediators** - **In children (aged 5-15), post streptococcal is most common (Group-A beta hemolytic strep)** - **Glomerular sclerosis (scarring)** - **Decreased glomerular perfusion (glomerular blood flow)** - **Decreased GFR** - **Thickening of the glomerular basement membrane with increased permeability to proteins and RBCs** - - - - - - - - **Clinical Sx:** - Sudden onset - Edema - HTN - Hypercoagulability - **Labs:** - **Proteinuria \>500 mg/day exceeding 3-5 g/day (protein is urine is never normal)** - Hematuria, brown-tinged urine - Lower serum albumin - Declining kidney fx, decreased GFR - **post infectious glomerulonephritis:** Inflammatory damage to glomerular basement membrane. 7-10d post strep infection in children. Adults post bacterial endocarditis or viral infections (varicella/hepatitis). - **Tx:** - Abx - Corticosteroids - Cytotoxic agents - Anticoagulants - - **Secondary causes:** - Diabetic neuropathy -- podocyte injury, progressive thickening/fibrosis of glomerular basement membrane - Lupus nephritis - **Clinical Sx:** - Proteinuria - Hypercholesterolemia - **Tx:** dialysis, transplant - - - - ***Glomerulonephritis is the most common cause of chronic kidney disease & end stage renal failure.*** **Hemolytic Uremic Syndrome** - **Most common community acquired cause of acute kidney failure in children (\31 - Frequently, increased creatinine levels - While Serum BUN levels are high -- patient will be asymptomatic or mildly symptomatic - **Uremia -- more symptomatic vs azotemia** - Syndrome of kidney failure - Retention of toxic wastes, deficiency states, electrolyte disorders - GFR \ glomerulonephritis **Acute Kidney Injury:** Sudden decline in renal function. ↓GFR, ↑BUN & Cr (nitrogenous waste). - A rise in serum creatinine concentration or a decline in urine output that developed within hours to days **Prerenal AKI:** - Cause=hypoperfusion (d/t emboli, cardiorenal syndrome, aortic dissection, renal vasoconstriction, cross clamping, hypovolemia) - No intrinsic damage - Initial onset = compensation by autoregulation and tubular feedback - Restoration of renal blood flow with IVF, hemodynamic support, and PRBCs can halt progression to intrarenal failure (ATN) - Avoid NSAIDs (renal prostaglandins mediate vasodilation in the kidney. NSAIDs reduce prostaglandin synthesis, causing renal vasculature constriction) **Intrarenal/Acute Tubular Necrosis (ATN)** - Most common cause of ARF in hospitalized patients (50%) - Intrinsic causes of ATN include ischemia and nephrotoxic drugs - The renal medulla is more susceptible to ischemic insult - The renal tubules use oxygen to support ionic transfer between tubules and peritubular fluid (poor oxygenation disrupts this mechanism) **Postrenal AKI:** - Cause = obstruction - Ex: clogged Foley, ureteral stones, neurogenic bladder - Obstruction causes increase in upstream hydrostatic pressures. Vasoconstriction & medullary hypoxia, renal tubular & interstitial edema, ↓GFR gradual. Clinical Manifestations: Hours of anuria🡪 flank pain🡪 remove obstruction🡪polyuria. Oliguria \