3 WHAT DO THE KIDNEYS DO?Extracts metabolic wastes from the blood stream and eliminates it from the bodyAdjusts blood pH by excretion of more or less acidAdjusts blood salt concentration by excretion of more or less saltAdjusts blood volume and blood pressure by secretion of renin (a hormone)Stimulates red blood cell production by excretion of erythropoietin (another hormone)
4 HOW DO THE KIDNEYS MANAGE TO DO ALL THESE THINGS? Due to the amazingly complex anatomy and physiology of the renal system!Now, a story…once upon a time there was a large salt water lake…
6 BLOOD FLOWS RED THROUGH THE GLOMERULUS So blood comes along with its toxins, glucose, amino acids, water, electrolytes, etc…enters the kidney via the renal arteryIt then enters afferent arterioles which take the blood into the glomerulus.The afferent arteriole contains the juxtaglomerular apparatus (causes renin to be excreted depending on the blood pressure)The glomerulus is the FILTER of the system. All water and small particles flow right through, but larger particles like sugar and protein can’t.So what makes it through the filter is filtered OUT of the bloodstream and moves into Bowman’s capsule and onto the tubular system…What doesn’t get filtered out continues on out the efferent arteriole, which is smaller than the afferent vessel in order to maintain a high pressure system for filtration.
9 THE TUBULAR SYSTEMSo the glomerular filtrate moves through the tubules where water and salts/electrolytes are exchanged between the tubular fluid and the blood vessels that run along the tubules.What is left over after all the exchanging is done is what is excreted = urine
11 THE TUBULESMost of the water is reabsorbed into the blood. ADH (anti-diuretic hormone) is secreted by the pituitary and controls how much or how little water is reabsorbed based on the osmolarity of the blood.Aldosterone (secreted by the adrenals) stimulates potassium to move from blood vessels into the tubule in exchange for sodium.The tubule reabsorbs all glucose and amino acids, but if there are too many glucose or AA particles, it can’t reabsorb them all spill into the urine.
13 URINE What is left over after all this occurs. Contains urea, creatinine (products of protein metabolism), toxins, and drug metabolites.Normal urine is acidic because energy metabolism creates acid which is eliminated in urine and in the breath (CO2)Urine also has sodium, potassium, electrolytes that vary depending on diet, exercise, hydration, and metabolism.Urine concentration varies according to the body’s need to conserve or excrete water to maintain normal blood osmolarity.
14 URINE Average urine output is 1-1.5 L/day. The kidney forms 180 L/day of filtrate.99% of what the glomerulus filters is reabsorbed by the tubules. (only 1% ends up as urine)It takes 30 min for all the body’s blood volume to be filtered.All the blood is cleaned about 50 times each day!
15 LABORATORY BUN = blood urea nitrogen If the kidneys aren’t working well, there will be more waste products higher BUN and creatinine in the blood.Urinalysis: dipstick, microscopy, cultureNitrite and leukocyte esteraseBilirubinColor/Specific gravityProteinGlucoseRed blood cellsKetonespH
16 Urinary System- Recap: Kidneys: produce urineExcretory duct systemUreter: conveys urine into bladder by peristalsisRenal pelvis: expanded upper portion of ureterMajor calyces: subdivisions of renal pelvisMinor calyces: subdivisions of major calyces into which renal papillae dischargeBladder: stores urineDischarges urine into urethra during voidingAnatomic configuration of bladder and ureters normally prevents reflux of urine into uretersUrethra: conveys urine from the bladder for excretion
17 Kidneys (1 of 2)Paired, bean-shaped organs below diaphragm adjacent to vertebral columnDivided into outer cortex and inner medulla (renal pyramids and columns)Excretory organs, functions along with lungs in excreting waste products of food metabolismThree basic functionsExcrete waste products of food metabolismCO2 and H2O: end-products of carbohydrate and fat metabolismUrea and other acids: end-products of protein metabolism that only the kidneys can excrete
18 Kidneys (2 of 2) Regulate mineral and H2O balance Excretes excess minerals and H20 ingested and conserves them as requiredBody’s internal environment is determined not by what a person ingests but by what the kidneys retainProduces erythropoietin and renin: specialized cells in the kidneysErythropoietin: regulates RBC production in marrowRenin: helps regulate blood pressure
19 Nephron (1 of 2) Basic structural and functional unit of the kidney About 1 million nephrons in each kidneyConsists of glomerulus and renal tubuleGlomerulusTuft of capillaries supplied by an afferent glomerular arteriole that recombine into an efferent glomerularMaterial is filtered by a 3-layered glomerular filterInner: fenestrated capillary endotheliumMiddle: basement membraneOuter: capillary endothelial cells (with foot processes and filtration slits)Mesangial cells: contractile phagocytic cells that hold the capillary tuft together; regulate caliber of capillaries affecting filtration rate
20 Nephron (2 of 2)Renal tubule: reabsorbs most of filtrate; secretes unwanted components into tubular fluid; regulates H2O balanceProximal end: Bowman’s capsuleDistal end: empties into collecting tubulesRequirements for normal renal functionFree flow of blood through the glomerular capillariesNormally functioning glomerular filter that restricts passage of blood cells and proteinNormal outflow of urine
21 The structure of the renal tubule, illustrating its relationship to the glomerulus and the collecting tubule.
23 Renal Regulation of Blood Pressure Renin: released in response to decreased blood volume, low blood pressure, low sodiumAngiotensin I → angiotensin II by angiotensin converting enzyme (ACE) as blood flows through the lungsAngiotensin II:Powerful vasoconstrictor: raises blood pressure by causing peripheral arterioles to constrictStimulates aldosterone secretion from adrenal cortex: increases reabsorption of NaCl and H2O by kidneysNet effect: higher blood pressure, increased fluid in vascular systemSystem is self-regulating
24 The role of the kidneys in regulation of blood pressure and blood volume.
25 RENAL VOCABULARY Anuria: little or no urine output Bacteriuria: bacteria in the urineDiuresis: increased urine outputDysuria: painful urinationGlycosuria: glucose in the urineHematuria: red blood cells in the urineNocturia: urination at nighttimeOliguria: less than normal urine outputPolyuria: more than normal urine outputProteinuria: protein in the urine
26 KIDNEY DISEASEHigh blood pressure and diabetes are both common causes of kidney disease.Kidneys collect, concentrate, and excrete toxins which can damage them over time.The renal tubules are very metabolically active and are therefore vulnerable to toxic damage and oxygen deprivation.
27 KIDNEY DISEASE Disease of one renal structure usually affects others. When there is a clinical abnormality, there are frequently several levels of the system that could have gone awry.Professional Guide to Diseases next slide
29 Congenital Anomalies Ch 7 Medullary sponge disease -Medullary sponge kidney is a benign congenital disorder characterized by dilatation of collecting tubules in 1 or more renal papillae, affecting 1 or both kidneys. Medullary sponge kidney is usually a benign condition, and patients can remain asymptomaticThe name medullary sponge kidney is misleading because the affected kidney does not resemble a sponge. The names tubular ectasia and cystic dilatation of the collecting ducts have been suggested as alternatives; however, medullary sponge kidney is the most commonly used name for this disorder.29
30 Congenital, continued Polycystic Kidney Disease Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited disorders in humans. It is the most frequent genetic cause of renal failure in adults, accounting for 6-8% of patients on dialysis in the United States.ADPKD is a multisystemic and progressive disorder characterized by the formation and enlargement of cysts in the kidney (as seen in the image below) and other organs (eg, liver, pancreas, spleen). Clinical features usually begin in the third to fourth decade of life, but cysts may be detectable in childhood and in utero30
31 Polycystic KidneyPain—in the abdomen, flank, or back—is the most common initial complaint, and it is almost universally present in patients with ADPKD (see Clinical). Ultrasonography is the diagnostic procedure of choice (see Workup). Medical therapy is needed to control problems such as hypertension, urinary tract infections, hematuria, and pain. Surgical drainage of cysts may be indicated. Patients who progress to end-stage renal disease (ESRD) may require dialysis or renal transplantation.31
32 Other Congenital Abnormalities Renal agenesis: failure of one or both kidneys to developBilateral: rare, associated with other congenital anomalies, incompatible with lifeUnilateral: common, asymptomatic; other kidney enlarges to compensateDuplications of urinary tractComplete duplication: formation of extra ureter and renal pelvisIncomplete duplication: only upper part of excretory system is duplicatedMalposition: one or both kidneys, associated with fusion of kidneys; horseshoe kidney; fusion of upper pole
34 AZOTEMIARenal failure manifest only by abnormal laboratory tests. No clinical signs of kidney failure are present. Usually elevated BUN and creatinine.
35 ACUTE RENAL FAILURE Acute oliguria or anuria plus azotemia Most common cause is damage to the renal tubules (acute tubular necrosis) that occurs during shock (with acute reduction in blood flow to the kidneys due to hemorrhage, infection).Other causes include tubular damage from medications or toxins (heavy metals, X-ray contrast), hemolysis or rhabdomyolysis (acute release of intracellular proteins that the kidneys have to filter but can’t). Also acute glomerular or vascular diseaseUsually the tubules can recover if the offending agent is identified and removed.
36 UREMIA Renal failure with clinical signs and symptoms. Hypertension (retention of salt and water)Anemia (low erythropoietin)Edema (retention of salt and water)Oliguria (low glomerular filtration rate)Accumulation of toxic metabolic waste products pericarditis, gastroenteritis, coagulation defects, neuropathy, encephalopathy
37 Renal Failure (Uremia) (1 of 2) Retention of excessive byproducts of protein metabolism in the bloodAcute renal failureCauses: tubular necrosis from impaired blood flow to kidneys or effects of toxic drugsRenal function usually returnsChronic renal failureFrom progressive, chronic kidney disease; > 50% from chronic glomerulonephritisOthers include congenital polycystic kidney disease, nephrosclerosis, diabetic nephropathy
38 Renal Failure (Uremia) (2 of 2) Clinical manifestationsWeakness, loss of appetite, nausea, vomitingAnemiaToxic manifestations from retained waste productsEdema: retention of salt and waterHypertensionTreatmentHemodialysis
39 URINARY TRACT INFECTION Bacteria and white blood cells in the urineInfection can be anywhere in the urinary tract from the kidneys to the urethra.Can be without symptoms or with dysuria and fever.Acute bladder inflammation (cystitis) is the most common. Risks: sex, catheterization, surgery, back-to-front wiping, urinary reflux, stonesPyelonephritis-usually due to ascended cystitis. Flank pain, fever, dysuria, frequency, urgency. Can lead to sepsis and renal failure.
40 Pyelonephritis Involvement of upper urinary tract from Ascending infection from the bladder (ascending pyelonephritis)Carried to the kidneys from the bloodstream (hematogenous pyelonephritis)Clinical manifestations: similar with an acute infectionLocalized pain and tenderness over affected kidneyResponds well to antibioticsCystitis and pyelonephritis are frequently associatedSome cases become chronic and lead to kidney failure
41 GlomerulonephritisInflammation of the glomeruli caused by antigen- antibody reaction within the glomeruliImmune-complex glomerulonephritisUsually follows a beta-streptococcal infection (APSGN)Circulating antigen and antibody complexes are filtered by glomeruli and incite inflammationLeukocytes release lysosomal enzymes that cause injury to the glomeruliOccurs in SLE; immune complexes trapped in glomeruliOccurs in IgA nephropathyAnti-glomerular basement membrane (anti-GBM) glomerulonephritis: autoantibodies attack glomerular basement membrane
42 Post-Strep Glomerulonephritis Acute glomerulonephritis is characterized by the sudden appearance of hematuria, proteinuria, red blood cell casts in the urine, edema, and hypertension with or without oliguria. It can follow streptococcal infections. This illness was first recognized as a complication of the convalescence period of scarlet fever in the 18th century. A link between hemolytic streptococci and acute glomerulonephritis was recognized in the 20th century. (see next two slides for definitions of hematuria and proteinuria, occult)
43 OCCULT HEMATURIAMicroscopic hematuria (can’t see the blood but there are red blood cells)May be caused by mild or early glomerular disease, or disease elsewhere in the urinary tract.A lot of times the cause is unknown
44 OCCULT PROTEINURIA Detectable only on urinalysis Small amounts of protein may be present with fever, with urinary tract infection, or following strenuous exercise.May be due to glomerular disease or renal damage from hypertension.
45 APSGNLatent periodA latent period always occurs between the streptococcal infection and the onset of signs and symptoms of acute glomerulonephritis.In general, the latent period is 1-2 weeks after a throat infection and 3-6 weeks after a skin infection.The onset of signs and symptoms at the same time as pharyngitis (also called synpharyngitic nephritis) is more likely to be immunoglobulin A (IgA) nephropathy rather than APSGN.Dark urine (brown-, tea-, or cola-colored)This is often the first clinical symptom.Dark urine is caused by hemolysis of red blood cells that have penetrated the glomerular basement membrane and have passed into the tubular system.45
46 APSGN Periorbital edema The onset of puffiness of the face or eyelids is sudden. It is usually prominent upon awakening and, if the patient is active, tends to subside at the end of the day.In some cases, generalized edema and other features of circulatory congestion, such as dyspnea, may be present.Edema is a result of a defect in renal excretion of salt and water.The severity of edema is often disproportionate to the degree of renal impairment.Nonspecific symptomsThese can include general malaise, weakness, and anorexia and are present in 50% of patients.Approximately 15% of patients complain of nausea and vomiting.46
47 ACUTE NEPHRITIC SYNDROME Acute nephritic syndrome presenting as edema, hematuria, and hypertension with or without oliguria is the most frequent presentation of APSGN. Approximately 95% of clinical cases have at least 2 manifestations, and 40% have the full-blown acute nephritic syndrome.Acute glomerular inflammation (glomerulonephritis)Causes hematuria, hypertension, azotemia, oliguria, and edemaAlmost always caused by acute autoimmune disease.The inflammation impairs blood flow through the glomerulus, reducing the filtration rate oliguria and causes leaking of red blood cells through it hematuriaNot much blood is getting through, so more renin is produced which causes high blood pressure.Can occur after strep throat when antibodies made to attack the strep also attack the glomerulus. Usually in kids and appear several weeks after the infection.
48 PE in APSGN Acute nephritic (last slide) Edema Hypertension Oliguria HematuriaLeft Ventricular Dysfunction48
49 Treatment in APSGNSymptomatic therapy is recommended for patients with acute poststreptococcal glomerulonephritis (APSGN), and it should be based on the clinical severity of the illness. The major goal is to control edema and blood pressure.Always consider Abx therapy for strep infections49
50 Renal Tubular Injury/Necrosis PathogenesisImpaired renal blood flowTubular necrosis caused by toxic drugs or chemicalsClinical manifestationAcute renal failure: oliguria, anuriaTubular function gradually recoversTreated by dialysis until function returns
51 ATNAcute tubular necrosis (ATN) is the most common cause of acute kidney injury (AKI) in the renal category. AKI is commonly defined as an abrupt decline in renal function, manifested by acute elevation in plasma blood urea nitrogen (BUN) and serum creatinine, occurring in hours to days to weeks, and usually reversible.51
52 ATN-Treatment Identify and remove the toxin Supportive care with fluids and electrolytes52
53 Urinary ObstructionBlockage of urine outflow leads to progressive dilatation of urinary tract proximal to obstruction, eventually causes compression atrophy of kidneysManifestationsHydroureter: dilatation of ureterHydronephrosis: dilatation of pelvis and calycesCausesBilateral: obstruction of bladder neck by enlarged prostate or urethral strictureUnilateral: ureteral stricture, calculus, tumorComplications: stone formation; infectionsDiagnosis and treatment: pyelogram, CT scan
54 NEPHROLITHIASIS Stones in the kidneys Grain of sand big enough to fill the renal pelvisMen > women, 20’s-30’sHematuria, colicky painCan occur once or be recurrentCalcium stones (75%): due to increased urinary calcium; hyperparathyroidismInfection stones/magnesium (15%): precipitate in alkaline environment created by infectionUric acid stones (5%): 25% of patients with gout form them, but most people with these stones don’t have gout
55 Urinary Calculi (1 of 3) Stones may form anywhere in the urinary tract Predisposing factorsHigh concentration of salts in urine saturates urine causing salts to precipitate and form calculiUric acid in goutCalcium salts in hyperparathyroidismUrinary tract infections reduce solubility of salts in urine; clusters of bacteria are sites where urinary salts may crystallize to form stoneUrinary tract obstruction causes urine stagnation, promotes stasis and infection, further increasing stone formation
56 Urinary Calculi (2 of 3)Staghorn calculus: urinary stones that increase in size to form large branching structures that adopt to the contour of the pelvis and calycesSmall stones may pass through ureters causing renal colicSome become impacted in the ureter and need to be removedManifestationsRenal colic associated with passage of stoneObstruction of urinary tract causes hydronephrosis- hydroureter proximal to obstruction
57 Urinary Calculi (3 of 3) Treatment Cystoscopy: snares and removes stones lodged in distal ureterShock wave lithotripsy: stones lodged in proximal ureter are broken into fragments that are readily excreted
60 NEPHROTIC SYNDROME Caused by various glomerulus problems Characterized by lots of protein in the urine (leaky, damaged glomerulus), low protein in the blood (due to loss in urine), edema (due to loss of protein).Diabetic kidney disease is a common cause. Also autoimmune disease which can be caused by Hep B, malaria, drugs, or cancers
61 GLOMERULAR DISEASEAtherosclerotic plaques form in the renal arteries reduce blood flow to the kidney atrophyHigh glomerular pressure in hypertension damages/scars glomeruli. Renin-angiotensin- aldosterone mechanism is triggered by reduced blood flow, which increases blood pressure even more.Vasculitis associated with autoimmune diseases (e.g. lupus) can also damage the glomerulus
62 Chronic Glomerulonephritis Nearly all forms of acute glomerulonephritis have a tendency to progress to chronic glomerulonephritis. The condition is characterized by irreversible and progressive glomerular and tubulointerstitial fibrosis, ultimately leading to a reduction in the glomerular filtration rate (GFR) and retention of uremic toxins. If disease progression is not halted with therapy, the net results are chronic kidney disease (CKD), end-stage renal disease (ESRD), and cardiovascular disease. The diagnosis of CKD can be made without knowledge of the specific cause62
63 Chronic Glomerulonephritis Dietary education is paramount in managing patients with CKD. The typical dietary restriction is 2 g of sodium, 2 g of potassium, and g of protein a day. Additional restrictions may apply for diabetes, hyperlipidemia, and fluid overload.Treatment is essentially supportive with the goal to keep blood pressure down and electrolytes normal, as well as preventing heart failure.63
64 Renovascular Hypertension RVH is the rise in systemic blood pressure resulting from stenosis of the major renal arteries or their branches or else from infrarenal atherosclerosis. The narrowing may be partial or complete and the resulting blood pressure elevation may be benign or malignant. (most common secondary hypertension)Stenosis or occlusion of the renal artery stimulates the affected kidney to release renin... recall the cascade.64
65 ConsiderationsOnset of hypertension occurring in patients younger than 30 years without risk factorsAbrupt onset of severe (stage II) hypertension (greater than 160/100 in patients older than 55 years)Severe or resistant hypertension despite appropriately dosed multidrug (>3 agents) antihypertensive therapyAbrupt increase in blood pressure over previously stable baseline in patients with previously well-controlled essential hypertension as well as patients with known RASNegative family history for hypertensionTwo major legs of treatment once underlying cause is identified is compliance on meds and smoking cessation65
66 HydronephrosisDefined as an abnormal dialtion of the renal pelvis and the calyces of one or both kidneys, caused by an obstruction of urine flow from the genitourinary tract.Caused by obstructive neuropathy like BPH, strictures, calculi, and congenital problemsSymptoms are those of UTI66
67 URINARY TRACT OBSTRUCTION Acute and chronicProstate enlargement, tumors, scars, stonesUrine stagnates, collecting system dilates above the obstruction, bacterial infection can occurCan lead to renal failure
68 CHRONIC RENAL FAILURELow urine output, prolonged symptoms and signs of renal failureEnd stage renal disease = burned out kidneys, shrunken, functionlessCauses: diabetes, chronic glomerulonephritis (anemia and fatigue, occult proteinuria, hypertension, edema), hypertension account for about 75% of cases.Can also be caused by chronic use of aspirin, acetaminophen, codeine, NSAIDs
69 DIALYSIS Used in both acute or chronic renal failure Can sustain patients even when their kidneys aren’t doing their job and the person would otherwise get quite sick and die.Hemodialysis creates a circuit of blood that passes from the body through a machine and back into the body again. In the machine blood passes through tubes with thin walls made of a semipermeable membrane that allows only certain substances to cross into and from blood. The patient’s blood is cleaned, the electrolytes and acid levels are balanced, and wastes are eliminated before sending the blood back into the patient’s body.Usually a patient is dialyzed 3 times a week. It takes 3-4 hours.
70 A NOTE ABOUT DIABETESDiabetic kidney disease is the most common cause of renal failure in the U.S.About 20% of patients with diabetes develop chronic renal failure.Glycoproteins deposit in glomerular capillaries and interfere with glomerular blood flow and damage the barrier function that prevents protein from entering the glomerular filtrate.
71 A note onTUMORS OF THE KIDNEY Most tumors of the kidney are malignantMore common with increasing ageRenal cell carcinoma: 90% of renal cancers, affects the epithelium of the tubules. Smokers have twice the risk. Flank pain, hematuria. Tx: removal of kidney