1. WESTERN CLINICAL MEDICINE
THE AMAZING KIDNEYS
WESTERN CLINICAL MEDICINE
SP 2012
Systems IV

2. THE URINARY SYSTEM

3. WHAT DO THE KIDNEYS DO?
Extracts metabolic wastes from the blood stream and eliminates it from the body
Adjusts blood pH by excretion of more or less acid
Adjusts blood salt concentration by excretion of more or less salt
Adjusts 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…

5. FIRST WE’LL MEET THE

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 artery
It 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 SYSTEM
So 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 TUBULES
Most 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, culture
Nitrite and leukocyte esterase
Bilirubin
Color/Specific gravity
Protein
Glucose
Red blood cells
Ketones pH

16. Urinary System- Recap:
Kidneys: produce urine
Excretory duct system
Ureter: conveys urine into bladder by peristalsis
Renal pelvis: expanded upper portion of ureter
Major calyces: subdivisions of renal pelvis
Minor calyces: subdivisions of major calyces into which renal papillae discharge
Bladder: stores urine
Discharges urine into urethra during voiding
Anatomic configuration of bladder and ureters normally prevents reflux of urine into ureters
Urethra: conveys urine from the bladder for excretion

17. Kidneys (1 of 2)
Paired, bean-shaped organs below diaphragm adjacent to vertebral column
Divided into outer cortex and inner medulla (renal pyramids and columns)
Excretory organs, functions along with lungs in excreting waste products of food metabolism
Three basic functions
Excrete waste products of food metabolism
CO2 and H2O: end-products of carbohydrate and fat metabolism
Urea 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 required
Body’s internal environment is determined not by what a person ingests but by what the kidneys retain
Produces erythropoietin and renin: specialized cells in the kidneys
Erythropoietin: regulates RBC production in marrow
Renin: helps regulate blood pressure

19. Nephron (1 of 2) Basic structural and functional unit of the kidney
About 1 million nephrons in each kidney
Consists of glomerulus and renal tubule
Glomerulus
Tuft of capillaries supplied by an afferent glomerular arteriole that recombine into an efferent glomerular
Material is filtered by a 3-layered glomerular filter
Inner: fenestrated capillary endothelium
Middle: basement membrane
Outer: 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 balance
Proximal end: Bowman’s capsule
Distal end: empties into collecting tubules
Requirements for normal renal function
Free flow of blood through the glomerular capillaries
Normally functioning glomerular filter that restricts passage of blood cells and protein
Normal outflow of urine

21. The structure of the renal tubule, illustrating its relationship to the glomerulus and the collecting tubule.

22. Bowman’s Capsule
© Courtesy of Leonard Crowley, M.D./University of Minnesota Medical School

23. Renal Regulation of Blood Pressure
Renin: released in response to decreased blood volume, low blood pressure, low sodium
Angiotensin I → angiotensin II by angiotensin converting enzyme (ACE) as blood flows through the lungs
Angiotensin II:
Powerful vasoconstrictor: raises blood pressure by causing peripheral arterioles to constrict
Stimulates aldosterone secretion from adrenal cortex: increases reabsorption of NaCl and H2O by kidneys
Net effect: higher blood pressure, increased fluid in vascular system
System 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 urine
Diuresis: increased urine output
Dysuria: painful urination
Glycosuria: glucose in the urine
Hematuria: red blood cells in the urine
Nocturia: urination at nighttime
Oliguria: less than normal urine output
Polyuria: more than normal urine output
Proteinuria: protein in the urine

26. KIDNEY DISEASE
High 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

28. CHAPTER 7 PGD Congenital Anomalies
medullary sponge disease and polycystic kidney disorder
Acute Renal Disorders
renal failure, pyelonephritis, poststreptococcal glomerulonephritis, tubular necrosis, renal infarction, renal calculi, renal vein thrombosis
Chronic Renal Disorders
nephrotic syndrome, chronic glomerulonephritis, renovascular hypertension, hydronephrosis, renal tubular acidosis, chronic renal failure
Lower Urinary Tract Disorders
lower UTI, vesicoureteral reflux, neurogenic bladder, congenital anomalies of ureter-bladder-urethra
Prostate and Epididymis Disorders
prostatitis, epididymitis, BPH 28

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 asymptomatic
The 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 utero 30

31. Polycystic Kidney
Pain—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 develop
Bilateral: rare, associated with other congenital anomalies, incompatible with life
Unilateral: common, asymptomatic; other kidney enlarges to compensate
Duplications of urinary tract
Complete duplication: formation of extra ureter and renal pelvis
Incomplete duplication: only upper part of excretory system is duplicated
Malposition: one or both kidneys, associated with fusion of kidneys; horseshoe kidney; fusion of upper pole

33. Acute Renal Disorders acute renal failure acute pyelonephritis
acute poststreptococcal glomerulonephritis
acute tubular necrosis
acute renal infarction- not covering
acute renal calculi
acute renal vein thrombosis-not covering

34. AZOTEMIA
Renal 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 disease
Usually 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 blood
Acute renal failure
Causes: tubular necrosis from impaired blood flow to kidneys or effects of toxic drugs
Renal function usually returns
Chronic renal failure
From progressive, chronic kidney disease; > 50% from chronic glomerulonephritis
Others include congenital polycystic kidney disease, nephrosclerosis, diabetic nephropathy

38. Renal Failure (Uremia) (2 of 2)
Clinical manifestations
Weakness, loss of appetite, nausea, vomiting
Anemia
Toxic manifestations from retained waste products
Edema: retention of salt and water
Hypertension
Treatment
Hemodialysis

39. URINARY TRACT INFECTION
Bacteria and white blood cells in the urine
Infection 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, stones
Pyelonephritis-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 infection
Localized pain and tenderness over affected kidney
Responds well to antibiotics
Cystitis and pyelonephritis are frequently associated
Some cases become chronic and lead to kidney failure

41. Glomerulonephritis
Inflammation of the glomeruli caused by antigen- antibody reaction within the glomeruli
Immune-complex glomerulonephritis
Usually follows a beta-streptococcal infection (APSGN)
Circulating antigen and antibody complexes are filtered by glomeruli and incite inflammation
Leukocytes release lysosomal enzymes that cause injury to the glomeruli
Occurs in SLE; immune complexes trapped in glomeruli
Occurs in IgA nephropathy
Anti-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 HEMATURIA
Microscopic 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. APSGN
Latent period
A 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 symptoms
These 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 edema
Almost 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  hematuria
Not 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
Hematuria
Left Ventricular Dysfunction 48

49. Treatment in APSGN
Symptomatic 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 infections 49

50. Renal Tubular Injury/Necrosis
Pathogenesis
Impaired renal blood flow
Tubular necrosis caused by toxic drugs or chemicals
Clinical manifestation
Acute renal failure: oliguria, anuria
Tubular function gradually recovers
Treated by dialysis until function returns

51. ATN
Acute 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 electrolytes 52

53. Urinary Obstruction
Blockage of urine outflow leads to progressive dilatation of urinary tract proximal to obstruction, eventually causes compression atrophy of kidneys
Manifestations
Hydroureter: dilatation of ureter
Hydronephrosis: dilatation of pelvis and calyces
Causes
Bilateral: obstruction of bladder neck by enlarged prostate or urethral stricture
Unilateral: ureteral stricture, calculus, tumor
Complications: stone formation; infections
Diagnosis and treatment: pyelogram, CT scan

54. NEPHROLITHIASIS Stones in the kidneys
Grain of sand  big enough to fill the renal pelvis
Men > women, 20’s-30’s
Hematuria, colicky pain
Can occur once or be recurrent
Calcium stones (75%): due to increased urinary calcium; hyperparathyroidism
Infection stones/magnesium (15%): precipitate in alkaline environment created by infection
Uric 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 factors
High concentration of salts in urine saturates urine causing salts to precipitate and form calculi
Uric acid in gout
Calcium salts in hyperparathyroidism
Urinary tract infections reduce solubility of salts in urine; clusters of bacteria are sites where urinary salts may crystallize to form stone
Urinary 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 calyces
Small stones may pass through ureters causing renal colic
Some become impacted in the ureter and need to be removed
Manifestations
Renal colic associated with passage of stone
Obstruction of urinary tract causes hydronephrosis- hydroureter proximal to obstruction

57. Urinary Calculi (3 of 3) Treatment
Cystoscopy: snares and removes stones lodged in distal ureter
Shock wave lithotripsy: stones lodged in proximal ureter are broken into fragments that are readily excreted

58. Large staghorn calculus of kidney

59. Next Section Chronic Renal Disorders
nephrotic syndrome, chronic glomerulonephritis, renovascular hypertension, hydronephrosis, renal tubular acidosis, chronic renal failure 59

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 DISEASE
Atherosclerotic plaques form in the renal arteries  reduce blood flow to the kidney  atrophy
High 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 cause 62

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. Considerations
Onset of hypertension occurring in patients younger than 30 years without risk factors
Abrupt 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 therapy
Abrupt increase in blood pressure over previously stable baseline in patients with previously well-controlled essential hypertension as well as patients with known RAS
Negative family history for hypertension
Two major legs of treatment once underlying cause is identified is compliance on meds and smoking cessation 65

66. Hydronephrosis
Defined 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 problems
Symptoms are those of UTI 66

67. URINARY TRACT OBSTRUCTION
Acute and chronic
Prostate enlargement, tumors, scars, stones
Urine stagnates, collecting system dilates above the obstruction, bacterial infection can occur
Can lead to renal failure

68. CHRONIC RENAL FAILURE
Low urine output, prolonged symptoms and signs of renal failure
End stage renal disease = burned out kidneys, shrunken, functionless
Causes: 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 DIABETES
Diabetic 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 malignant
More common with increasing age
Renal cell carcinoma: 90% of renal cancers, affects the epithelium of the tubules. Smokers have twice the risk. Flank pain, hematuria. Tx: removal of kidney