Notes:                    Pathology
Notetaker:                Roy, S. pgs 20
Term:                     Spring 2006
Lecture...
Secretion of hormones
1. Secretion of erythropoietin, which regulates red blood cell production in the bone marrow.
2. Se...
corpuscle, which is composed of a glomerulus enclosed in a Bowman's capsule.

Cells, proteins, and other large molecules a...
QuickTimeª and a
                               TIFF (Uncompressed) decompressor
                                 are need...
3. large burns
   4. crushing injuries
   5. toxic exposure
          a. any chemical that precipitates at a low pH is nep...
Pathogenesis of ATN:
Key: decreased renal perfusion from preglomerular vasoconstrictionleakage of
tubular fluid into the ...
casts from Loop through collecting ducts. This is easier to understand if you look at Alide
103
.
Four Clinical Phases of ...
Involves inflammation and fibrosis in tissue space
results in chronic renal failure

Pyleonephritis
Let’s bk it down: “...
3. hormonal cycles affect "bacterial adherence"
   4. "honeymoon" cystitis
         a. aggressive, frequent or sex without...
b. frequency
          c. urgency
   3. systemic evidence of infection
   4. leukocyte casts in urine is diagnostic

Predi...
2. Reflux Nephropathy (VUR)
         a. By far the more common form of CPN scarring; occurs in childhood as the
          ...
How Toxins Renal Injury
         1. interstitial immune reactions (hypersensitivity)
         2. direct tubule damage (e....
inhibiting the vasodialatory effects of PGE, predisposing the papillae to ischemia.

The papillary necrosis is distinguis...
See slide 133/163 for a picture of urate crystals

2.       Chronic urate nephropathy is assoc with
     •   deposition of...
Neoplastic causes of renal interstitial disease
   1. nonrenal malignant tumors, esp. hemopoietic impact the kidney inters...
Malignant nephrosclerosis
is the form of renal dz assoc with the accelerated phase of HT. It is a Frequent cause of
death ...
Renal Artery Stenosis
a)     most often caused by an atheroma at origin of renal artery
b)     which causes increased ren...
•   cardiovascular damage

Adult hemolytic uremic syndrome
Can occur in a variety of settings by mechanisms that are not c...
3. emboli from heart
4. thrombosis because of PAN

See Slide 155/163 for a nice pic of this.

URINARY OBSTRUCTION
Definiti...
(a) hypercalcemia
       (b) may cause nephrocalcinosis too

Morphology
  • often multiple sites
  • most at poles of kidn...
7. Often see pulmonary metastasis but with chemotherapy and radiation has a 90%
     long term survival

End:wk7PathMPart ...
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Notes: Pathology

  1. 1. Notes: Pathology Notetaker: Roy, S. pgs 20 Term: Spring 2006 Lecturer: Frederickson Topic: Kidney Part IV Date: Monday, May 15, 2006 Class Bulletin: The notes enclosed include the intellectual property of Dr. Rich Fredrickson. For this reason, they may not be copied, reproduced, altered or used in any way for profit without the written consent of said lecturer. Dr. Fredrickson can be reached at 425 602 3155 or RFREDRIC@bastyr.edu for further questions. Outline for this lecture Topic: Kidney Part IV Physiology review DISEASES THAT AFFECT THE TUBULES Acute Tubular Necrosis DISEASES THAT AFFECT THE INTERSTITIUM Pyleonephritis Acute Pyleonephritis Chronic Pyelonephritis and Reflux Nephropathy Drug Induced Nephritis Analgesic Nephritis Metabolic Nephropathy Neoplasms DISEASES OF RENAL BLOOD VESSELS Benign Hypertension and Nephrosclerosis Malignant Hypertension and Nephrosclerosis Renal Artery Stenosis Thrombotic Microangiopathies Other Vascular Diseases of the Kidney URINARY OBSTRUCTION UROLITHIASIS NEOPLASMS OF THE KIDNEY Benign Malignant Topic: Kidney Part IV Physiology review: I don’t know about you but I am getting lost in all the terminology. I just want to make sure that I understand, when reviewing renal path, it is useless to memorize and far more important to understand the normal function and anatomy of the kidney and then piece out by the NAME of the pathology what may go wrong. For example, in studying “Acute Tubular Necrosis” I need to understand what renal tubules are, how they work and what they do. Then, piece out the name: Acute, sudden and severe onset. Tubular: dz occurring in the renal tubules. Necrosis: death of cells. “translation: suddenly, the cells in renal tubules begin to die.” From this, I know that the etiology has to be ischemia or toxic exposure, and that necrosis will lead to renal failure! For my own sake, I am going to review the physiology in brief. This was mostly covered in Kidney Part I; feel free to skip this. FUNCTIONS OF THE KIDNEY Filtration of wastes The kidney removes from the blood many organic wastes, ammonia, urea, and other metabolic byproducts that may otherwise be harmful to the body. 1
  2. 2. Secretion of hormones 1. Secretion of erythropoietin, which regulates red blood cell production in the bone marrow. 2. Secretion of renin, which is a key part of the renin-angiotensin-aldosterone system. 3. Secretion of the active form of vitamin D, calcitriol, and prostaglandins. Sodium and water homeostasis There is a stable balance of sodium and water in the body. The major homeostatic control point for maintaining this stable balance is renal excretion. The kidney is directed to excrete or retain sodium via the actions of: 1. aldosterone 2. antidiuretic hormone (ADH, or vasopressin) 3. atrial natriuretic peptide (ANP) on it. Acid-base homeostasis The body is very sensitive to its pH level. Outside the range of pH that is compatible with life, proteins are denatured and digested, enzymes lose their ability to function, and the body is unable to sustain itself. The kidneys maintain acid-base homeostasis by regulating the pH of the blood plasma. Gains and losses of acid and base must be balanced. Sources of acid gain: • Carbon dioxide (since CO2 and H2OH2CO3, carbonic acid, with catalyst: carbonic anhydrase) • Metabolism of proteins and other organic molecules Production of nonvolatile acids • Diarrhea or urine Loss of bicarbonate Sources of acid loss: Metabolism of various organic anions Use of hydrogen ions Vomit or urine Loss of acid When acid loss > acid gain  alkalosis When acid gain >acid loss  acidosis Kidney Responses to acidosis: 1. Bicarbonate is added to the blood plasma by tubular cells. 2. Tubular cells reabsorb more bicarbonate from the tubular fluid 3. Collecting duct cells secrete more hydrogen and generate more bicarbonate. 4. Ammoniagenesis leads to increased buffer formation (in the form of NH3) Kidney Responses to alkalosis: 1. Excretion of bicarbonate in urine. a. This is caused by lowered rate of hydrogen ion secretion from tubular epithelial cells. b. This is also caused by lowered rates of glutamine metabolism and ammonia excretion. Buffering of hydrogen ions Any substance that can reversibly bind hydrogen ions is called a buffer. Hydrogen ions are buffered by extracellular (e.g., bicarbonate) and intracellular buffers (including proteins and phosphate). MECHANISMS OF THE KIDNEY The kidney's ability to perform many of its functions depends on the three fundamental functions of filtration, reabsorption, and secretion. Filtration The blood is filtered by nephrons, the functional units of the kidney. Each nephron begins in a renal 2
  3. 3. corpuscle, which is composed of a glomerulus enclosed in a Bowman's capsule. Cells, proteins, and other large molecules are filtered out of the glomerulus by a process of ultrafiltration, leaving an ultrafiltrate that resembles plasma (with negligible plasma proteins) to enter Bowman's space. Filtration is driven by Starling forces. The ultrafiltrate is passed through, in turn, the proximal tubule the loop of Henle the distal convoluted tubule and a series of collecting ducts to form urine. Reabsorption Tubular reabsorption is the process by which solutes and water are removed from the tubular fluid and transported into the blood. It is called reabsorption (and not absorption) because these substances have already been absorbed once (particularly in the intestines). Reabsorption is a two-step process beginning with the active or passive extraction of substances from the tubule fluid into the renal interstitium (the connective tissue that surrounds the nephrons), and then the transport of these substances from the interstitium into the bloodstream. These transport processes are driven by Starling forces, diffusion, and active transport. In some cases, reabsorption is indirect. For example, bicarbonate (HCO3-) does not have a transporter, so its reabsorption involves a series of reactions in the tubule lumen and tubular epithelium. It begins with the active secretion of a hydrogen ion (H+) into the tubule fluid via a Na/H exchanger: And now for some Modell 3rd qtr Physio, or Littleton/ Biochem: In the lumen • The H+ combines with HCO3- to form carbonic acid (H2CO3) • Luminal carbonic anhydrase enzymatically converts H2CO3 into H2O and CO2 • CO2 freely diffuses into the cell In the epithelial cell • Cytoplasmic carbonic anhydrase converts the CO2 and H2O into H2CO3 • H2CO3 readily dissociates into H+ and HCO3- • HCO3- is facilitated out of the cell's basolateral membrane Some key regulatory hormones for reabsorption include: 1. aldosterone, which stimulates active sodium reabsorption, and 2. antidiuretic hormone, which stimulates passive water reabsorption Both hormones exert their effects principally on the collecting ducts. 3
  4. 4. QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture. Secretion Tubular secretion is the transfer of materials from peritubular capillaries to renal tubular lumen. Tubular secretion is caused mainly by active transport. Usually only a few substances are secreted. These substances are present in great excess, or are natural poisons. DISEASES THAT AFFECT THE TUBULES As we went over in Kidney Part I, in terms of disease, the kidney can be divided into four components: 1. Glomeruli a. filtration dz b. these are the most critical 2. Tubules a. dz of reabsorption 3. Interstitum a. Dz of connective tissue 4. Blood vessels a. Vascular disease We covered the most critical type of kidney pathology, Glomerular Disease. in Part III, now we will briefly address the rest: tubular, interstitial and vascular dz Acute Tubular Necrosis This is an acute destruction of the renal tubular epithelial cells that is a major cause of acute renal failure and severe oliguria (scant urine production) Major causes of ATN 1. ischemia (esp after shock) 2. bacterial septicemias 4
  5. 5. 3. large burns 4. crushing injuries 5. toxic exposure a. any chemical that precipitates at a low pH is nephrotoxic bc it’s high concentration affects the tubules The website: http://www.atsdr.cdc.gov/ from the CDC tells you where you find nephrotoxins and how to avoid them The nephrotoxic chemicals that are esp damaging to PCTs are: 1. heavy metals 2. mercury a. High: shark, bluefin tuna, orang roughy b. Low: salmon, canned tuna, shellfish 3. lead 4. gold 5. uranium 6. chromium 7. bismuth 8. platinum The nephrotoxic organic solvents are: 1. carbon tetrachloride a. It was used in the production of refrigeration fluid and propellants for aerosol cans, as a pesticide, as a cleaning fluid and degreasing agent, in fire extinguishers, and in spot removers. Because of its harmful effects, these uses are now banned and it is only used in some industrial applications. But it is still in the air, water and soil near industrial areas. 2. Chloroform a. Swimming pools 3. methyl alcohol 4. phenol a. You may be exposed to very low levels in your home because it is found in a number of products, including some medicines, lotions, and ointments. Low levels of phenol are found in some foods, including smoked summer sausage, fried chicken, mountain cheese, and some species of FARMED fish (eg salmon). Phenol enters the lungs when you inhale tobacco smoke. It can be present in low levels in air and drinking water. The nephrotoxic drugs are: 1. gentamycin 2. neomycin 3. aminoglycosides (abx against gram negative bacteria) 4. cyclosporin A 1. anti-rejection transplant drug 5
  6. 6. Pathogenesis of ATN: Key: decreased renal perfusion from preglomerular vasoconstrictionleakage of tubular fluid into the tissue spaceoliguria. 50% of acute renal failure in hospitals due to ATN. It is a reversible renal lesion… Caused by: 1. ischemia, primarily 2. nephrotoxic tubular obstruction due to casts or edema Steps in ischemia Step One Shock Step Two Volume of bld entering afferent arteriole drops Step Three Afferent in kidneyrenin Step Four Cleaves angiotensin from liverangiotensin I Step Five LungACE Step Six Cleaves angiotensin III Step Seven Angiotensin II causes systemic vasoconstriction of arterioles Step Seven With afferent arteriole constricted, there is further decreased perfusion Step Eight Decreased renal blood flow to peritubular caps drops Step Nine Tubular cells can’t make enough ATP Step Ten Loss of cell polarity Step Eleven Na rushes in distal tubulefeedback vasoconstrictionaggravates situ Step Twelve Necrosis of epithelial cells Step Thirteen Dead cells and protein slough off and “casts” plug up tubule Step Fourteen The high P in the lumen forces fluid out into tissue space Step Fifteen Obstructional debris further decreases GFR and tubular flow Step Fifteen Oliguria Steps in Tubular Obstruction Step One poisons directly interfere with ATP Step Two Loss of cell polarity Step Three Na rushes in distal tubulefeedback vasoconstrictionaggravates situ Step Four Extensive necrosis of PCT cells because low ATP production Step Thirteen Dead cells and protein slough off and “casts” plug up tubule Step Fourteen The high P in the lumen forces fluid out into tissue space Step Fifteen Obstructional debris further decreases GFR and tubular flow Step Fifteen Oliguria Figure 20-32 in the text, p994 is a really beautiful schematic that covers the entire pathogenesis in acute renal failure. P993-5 are a good read of the pathogenesis of ischemia. And Slides 103-4/163 give a diagram representation of tubular injury. It is important to note that ischemic injury causes patchy necrosis in PCT and Loop of Henle and casts from Loop through Collecting ducts. Whereas Toxic injury causes continous necrosis just distal to glomerulus through proximal tubule and proximally in PCT with 6
  7. 7. casts from Loop through collecting ducts. This is easier to understand if you look at Alide 103 . Four Clinical Phases of ATN Phase One Stage of onset (about 36 hours) with hypotension and shock Phase Two 1. Oliguric stage a. down to 40 to 400mls per day 2. uremia 3. hyperkalemia a. high potassium in the bloodstream 4. elevated BUN not excreted in urine, so bldg up 5. elevated serum creatinine not excreted in urine, so bldg up 6. metabolic acidosis a. increase in total body acid induced by 2 basic mechanisms, as follows: an inability of the kidneys to excrete the dietary hydrogen (H+) load, and an increase in the generation of H+ that is due to the addition of H+ (lactic acid or ketoacids) or to the loss of bicarbonate (HCO3-) due to inappropriate wasting by the kidney or the gastrointestinal tract. Phase Three 1. early diuretic phase b. increasing urine volume may reach 3 liters per day c. loss of electolytes, now hypokalemia d. may cause death because of severe electrolyte loss 1. also increased vulnerability to infections Phase Four 1. late diuretic phasenow in the third week 2. person survives shock, renal tubule cells start to regen 3. tubule anatomy and function is restored 4. BUN returns to normal 5. complete recovery DISEASES of THE RENAL INTERSTITIUM Basic features of Renal Interstital Dz Tubular dz primarily affects reabsorption. Reabsorption is a two-step process beginning with the active or passive extraction of substances from the tubule fluid into the renal interstitium. The interstitium is the connective tissue that surrounds the nephrons, so renal interstitial disease occurs along with renal tubular disease. Some glomerular involvement may be present 7
  8. 8. Involves inflammation and fibrosis in tissue space results in chronic renal failure Pyleonephritis Let’s bk it down: “pyelo” comes from the Greek word for pelvis. “nephritis” , Nephros, Gk for kidney, and “itis”, inflammation. So “pyleonephritis” is inflammation of the renal pelvis. What can I assume? The renal pelvis is connected to the ureter which is connected to the bladder which is connected to the urethra. Etiology probably involves some exogenous bacterial agent. What else? The function of the renal pelvis is to collect the urine formed and dumped by the collecting ducts. The cortical collecting ducts receive filtrate from multiple connecting tubules and descend into the renal medulla  medullary collecting ducts. The terminal portions of medullary ducts are papillary ducts renal papilla  into a minor calyxmajor calycesrenal pelvis. So a disease of the pelvis can travel up the calyces to the papilla and even affect the renal tubules and tissue surrounding them. General features of PN Very common disease affecting interstitial connective tissue, tubules and renal pelvis. Two main types of PN 1. acute a. always bacterialascending urinary tract infection 2. chronic a. may be caused by chronic infection b. may be associated with obvious obstruction Etiology and pathogenesis PN 1. gram negative bacilli a. 85% of cases 2. fecal flora a. E coli b. Proteus c. Klebsiella d. Enterobacteria 3. blood stream origin a. for example during septicemias b. esp seen if kidney is already compromised 4. obstructions i. constriction along urethra 1. Benign Prostate Hyperplasia ii. tumors of bladder iii. stones Most common path Ascending infections from a UTI especially in females where 8 X more likely than male. This is due to: 1. shorter urethra 2. no prostatic antimicrobial secretions 8
  9. 9. 3. hormonal cycles affect "bacterial adherence" 4. "honeymoon" cystitis a. aggressive, frequent or sex without psychological reception, sense of ‘owning it’, enjoyment/lubrication irritates urethra, and inflammation predisposes to infection Aggravation to common pathanything contributing to urine retention predisposes to principles of "vesicoureteral" reflux. Normally, in an adult, the ureters pass obliquely into the bladder (in kids, the passage is more direct, perpendicular). The oblique passageway allows for a VU valve. When the bladder is full, the P inside pushes on the tissue and closes the bladder (in kids, there is a greater risk of reflux). Least common pathobstructions and hematogenous infection. See Slide 112/163 for a digramatic representation of etiology in pyelo. See slide 113/163 for extra features of Pyelo Acute Pyleonephritis Acute pyelo is an acute pus-sy inflammation of the kidney caused by bacterial and sometimes viral infection, whether septic or ascending and associated with VU reflux. Morphology • acute interstitial suppurative inflammation • plus tubular coagulation necrosis (and pus in tubules) • focal abscesses especially on cortical surfaces+++++++ • GLOMERULI SEEM RESISTENT TO INFECTION Uncompliated APN usu benign course and S/Sx disappear in a few days after abx Tx. Complications of APN the three P’s 1. papillary necrosis a. esp in diabetics with decreased resistance 2. pyelonephrosis a. renal pelvis is a sac of pus 3. perinephric abscess a. rupture through capsule See Slide 115/163 for a really horrible picture of APN. Slide 116 is a histo slide that shows how APN is marked by acute neutrophilic exudate within the renal tubules and the renal substance and Slide 117 shows papillary necrosis—it’s pretty extraordinarily focal and uniform! Clinical course of APN 1. costovertebral angle tenderness 2. evidence of bladder irritation a. dysuria 9
  10. 10. b. frequency c. urgency 3. systemic evidence of infection 4. leukocyte casts in urine is diagnostic Predisposing conditions for APN 5. obstuctions 6. instrumentation 7. vesicoureteral reflux (VUR) 8. pregnancy 9. pre-existing renal lesions 10. patients sex and age 11. diabetes Chronic Pyelonephritis and Reflux Nephropathy Of course, here we are talking about chronic inflammation of the renal pelvis extending to the calyces, tubules and interstitium renal scarring. In CPN, the role of bacteria is uncertain. The two principle forms of CPN: 1. chronic obstructive a. obstruction (like a renal stone or cancer) causes high pressure backflow b. major and minor calyces are dilated like balloons c. P backflow into collecting ducts i. LEADS to: 1. "thyroidization" of the tubules a. pink debris or precipitated filtrate that can’t be removedtubules look like thyroid follicles: pathonumonic for CPN b. expanded epithelium in tubule with flat, proliferating cells instead of neat, sharp cuboidals, lined up. 2. P atrophy around the inside surface of the kidney 3. diffuse corticomedullary scars and atrophic cortex 4. CHRONIC renal failure 10
  11. 11. 2. Reflux Nephropathy (VUR) a. By far the more common form of CPN scarring; occurs in childhood as the result of a superimposition of UTI, a short intramural ureter and congenital vesicouretral reflux. It is a common source of hypertension in kids. b. RESULTS in: i. scars at upper and lower poles ii. scars over dilated minor calyces iii. lymphoid follicles at edge of calyx iv. arcuate and interlobular arteries show damage v. thyroidization of tubules c. EVENTUALLY i. Focal segmental glomerulonephritis Clinical features of CPN • back pain • fever • pyuria o pus-sy urine • bacturia • polyuria o signifies tubular involvement • proteinuria o signifies glomerulonephritis Drug Induced Nephritis What I can deduce from the name? Kidney inflammation due to toxic metabolites and or immune reactions from/to drug use/ abuse. Has to be hematogenous in origin, no one is sticking a drug up their ureter…I hope! Basic features • Renal exposure to drugs is high because of intense blood supply • Toxins insoluble at acid pH are precipitated in DCT and collecting ducts 11
  12. 12. How Toxins Renal Injury 1. interstitial immune reactions (hypersensitivity) 2. direct tubule damage (e.g., mercuric chloride) 3. subtle cumulative damage over many yearschronic renal insufficiency Allergic or Drug-induced nephritis These drugs: 1. nonsteroidal anti-inflammatory agents 2. synthetic penicillin 3. sulfonamides BUT not dose dependent damage CAUSE interstitial inflammation Clinical Signs and Symptoms: • Skin rash • eosinophilia • IgEs in serum • IgGs in tubular basement membrane • sometimes granulomas • hematuria • sterile pyuria+++++++ o NO BUGS, just pus. Clinical note: you want to drink LOTS of water when taking these drugs because you may be able to prevent tubular precipitation by dilution. Analgesic nephritis These DRUGS: • mixtures of analgesics o “coal tar analgesics”, antipyretics, usu mixtures of caffeine, aspirin, acetominophen (a less toxic metabolite of phenacetin), and codeine. • phenacetin (3 kg over 3 year span) o since it was demo’d to be carcinogenic it has been reformulated since 1983, it is an antipyretic analgesic RESULT in • papillary necrosis first • cortical-tubular-interstitial inflammation and fibrosis is secondary Pathogenesis of AN: Phenacetin metabolite acetominophen injures cells by: covalent bonding oxidative damage Aspirin potentiates this effect by: 12
  13. 13. inhibiting the vasodialatory effects of PGE, predisposing the papillae to ischemia. The papillary necrosis is distinguished from the acute necrosis in diabetics in that it is not uniform, one papillae can be necrotic and another fine. Morphology Analgesic Nephritis 1. Although most glomeruli are normal 2. We see early patchy necrosis of loops of Henle 3. eventually the collecting ducts and entire pyramid 4. reaches the papillae 5. detached or sloughed papillae (into urine) 6. dystrophic calcification is common o non systemic mineralization of soft tissue 7. Finallycortical atrophy and DIFFUSE INTERSTITIAL FIBROSIS 8. We also see analgesic microangiopathy o BM in blood vessel wall is split Clinical features of Analgesic Nephritis • "middle-aged women with chronic headaches" • inability to concentrate the urine • renal stones • pyuria • sloughed papillae may obstruct ureter • increased risk of papillary carcinoma of renal pelvis Metabolic Nephropathy Metabolic cause of renal interstitial disease • Urate nephropathy o urate crystals in interstitium and/or tubules o due to conditions leading to elevated levels of uric acid in blood like:  primary gout  polycythemia or leukemia  chemotherapy for cancer • causes sudden increase in uric acid from necrosis of cancer cells acute urate nephropathy  chronic lead poisoning URIC ACID METABOLISM Three types of nephropathy can occur in pats with hyperuremic disorders: 1. Acute urate nephropathy is assoc with • acid pH  precipitation of uric acid in collecting ducts leading to obstructions  acute renal failure • mostly seen in cancer pats 13
  14. 14. See slide 133/163 for a picture of urate crystals 2. Chronic urate nephropathy is assoc with • deposition of crystals of monosodium urate in distal tubules, collecting ducts and interstitiumlook needle-like in histo slide. • Mostly seen in protracted gout 3. Nephrolithiasis • Uric acid stones in 20% of patients with chronic gout • Uric acid stones in 40% of patients with acute urate nephropathy See slide 135/163 for a disturbing pic of the gross kidney with nephrolithiasis. Staghorn calculi (struvite stones) are a type of kidney stone that may occur with frequent kidney infections. They are called "staghorn" calculi because on X-rays they look like deer (stag) horns. Fewer than 10% of the people who have kidney stones have this type of stone. Struvite stones can be more serious because they are large stones and an infection may be present. Medical treatment, including antibiotics and surgical removal of the stone, is usually needed. Women are affected more than men because of their higher risk for urinary tract infections. CALCIUM/ POTASSIUM METABOLISM Nephrocalcinosis Dz char by hypercalcemia like: hyperparathyroidism multiple myeloma Vitamin D intoxication metastatic bone dz excess calcium intake RESULTs in: calcium phosphate in renal tubulescalcium stones. Basement membranes calcify in tubules and glomerulus Hypokalemic nephropathy Dz char by low potassium: GI tract disease adrenal overactivity chronic use of diuretics RESULTs in: interference with countercurrent exchange system in loops  disturbed tubular concentration of urine Neoplasms 14
  15. 15. Neoplastic causes of renal interstitial disease 1. nonrenal malignant tumors, esp. hemopoietic impact the kidney interstitum a. via paraneoplastic syndromes b. via therapy for cancer 2. multiple myeloma a. renal involvement occurs in 59% of patients with multiple myeloma b. tubules toxic to Bence-Jones proteins c. BJ proteins combine with certain glycoprotein to form casts d. progression to chronic renal failure or sometimes acute RF e. associated amyloidosis is common See slide 138/163 for a picture of myeloma kidney casts. Read more about this condition on p1005-6 of text. DISEASES OF RENAL BLOOD VESSELS We breezed through this in class. I am just pasting the notes here, I am going to just review pgs 1006-1012 for details. Benign Hypertension and Nephrosclerosis Definitions In looking at benign vs malignant pay attn to arterioles Benign hypertension Long term developing hypertensionhyaline arteriolosclerosis (from leakage of plasma proteins ) appears in renal vessels, loweres lumen size a tad and causes BENIGN NEPHROSCLEROSIS. Benign Nephrosclerosis Benign nephrosclerosis is the term used for the renal path assoc with sclerosis of renal arterioles and small arteries. The result is focal ischemia to tubules, glom and b membrane, narrow lumen and duplication of internal elastic membrane Note: benign nephrosclerosis rarely causes uremia Ischemic changes in nephrosclerosis • atrophy of tubules • glomerular ischemia and changes • collagen in Bowman's space • damage to GBM • possible total sclerosis of glomeruli Malignant Hypertension 220-240/13-140 mmHg 15
  16. 16. Malignant nephrosclerosis is the form of renal dz assoc with the accelerated phase of HT. It is a Frequent cause of death by uremia. It occurs in chronic renal failure and results in: hyperplastic arteriolosclerosis (onion-skin layers) fibrinoid necrosis in vessels high renin activity extrarenal complications. Extra renal Complications of Malignant HT: 1. LEFT VENTRICULAR FAILURE • increased intracranial pressure • headaches • nausea and vomiting • scotomas in visual fields • microaneurysms in retinal vessels 2. HYPERTENSIVE CRISIS • loss of consciousness • convulsions • medical emergency See slide 140 and 141 to compare hyaline to hyperplastic AS. Essential HT There are Two Etiology “classes” for Hypertension: 1. Essential or Primary 2. Secondary A person with HT 2ndary to Renal, Endocrine, Vascular, or Neurogenic probs will A person who has idiopathic high BP (140/90) and it is creeping up has essential HT. If left untreated, it will be expressed as arteriosclerosis in the kidney. 90-95% of those with malignant HT started out with essential HT. characteristics of essential HT: (1) females more (2) blacks more (3) about 50% of population over 50 (4) slow progression (5) leads to cardiovascular and cerebrovascular complications (6) is expressed as arteriolosclerosis even in kidney (7) possibly due to a defect in sodium excretion Pathogenesis of HT: Review slides 145-148: Important review of the pathogenesis of HT 16
  17. 17. Renal Artery Stenosis a) most often caused by an atheroma at origin of renal artery b) which causes increased renin secretion This is the most curable form of hypertension, remove the stenosis, remove the HT. Thrombotic Microangiopathies I’ll sound this title out: An occlusive (thrombotic) event in small bld vessels—this would result in hemolytic anemias in small vessels, thrombocytopenia and possibly renal failure… The text classifies thrombotic microangiopathies as follows: 1. Classic childhood HUS 2. Adult HUS 3. Familial HUS 4. Idopathic TTP There is considerable overlap between HUS and TTP, in fact, sometimes they are referred to as HUS/TTP. Childhood hemolytic uremic syndrome Uncommon but causes acute renal failure in kids S/Sx: • sudden severe oliguria • sudden severe hemolytic anemia Pathogenesis of these disorders is basically the same: Although these disorders may have diverse causes, two processes dominate the pathogenetic sequence of events: 1. endothelial injury and activation with subsequent intravascular thrombosis 2. platelet aggregation Both of these events cause: 1. vascular obstruction or microthrombi in glom caps 2. vasoconstriction ischemia Causes have been: 1. a strain of E coli from Jack-in-the-Box 2. or a Shiga toxin from Shigella Complications can include: • other thrombotic and bleeding problems • neurological damage 17
  18. 18. • cardiovascular damage Adult hemolytic uremic syndrome Can occur in a variety of settings by mechanisms that are not clear 1. Pregnancy with complications a. postpartum renal failure 2. Infection a. typhoid fever 3. oral contraceptives 4. vascular renal dz a. malignant HT 5. chemotherapeutic and immunosuppressive drugs Thrombotic thrombocytopenia purpura (TTP) It is caused by an acquired or genetic defect in a protease that cleaves large vWF multimers. The abnormal forms of vWF promote platelet aggregation. Slide: 152/163: Fibrin stain showing platelet-fibrin thrombi (red) in the glom caps, characteristic of microangiopathic disorders. On micro exam, the glomeruli show thickening and sometimes splitting of cap walls due to endothelial swelling and deposits of fibrin-related materials in the capillary lumen. Other Vascular Diseases of the Kidney Emboli from atheromatous plaques in aorta or renal artery the elderly with severe atherosclerosis Sickle cell nephropathy viscosity of blood through vasa recta hypoxia in renal medulla from too many sickled cells papillary necrosis Clinical note: papillary necrosis is seen in: • diabetics • pyelonephritis • analgesic nephropathy Renal infarction The kidney are favored sites for the development of infarcts. Contributing to this predisposition is the extensive bld flow to the kidneys (1/4) of cardiac output; but more important is the “end-organ” nature of the bld supply with limited collateral circulation from extra renal sites. Keys to remember: 1. no dual blood supply 2. wedge-shaped infarcts 18
  19. 19. 3. emboli from heart 4. thrombosis because of PAN See Slide 155/163 for a nice pic of this. URINARY OBSTRUCTION Definition: "hydronephrosis" Abnormal enlargement of a kidney, which may be caused by blockage of the ureter (such as by a kidney stone) or chronic kidney disease that prevents urine from draining into the bladder. Causes dilation of renal pelvis and calyces due to obstruction of outflow along with atrophy of renal tissue. May be unilateral or bilateral. May cause acute renal failure if bilateral. UROLITHIASIS A. in renal pelvis and calyces B. calcium oxalate C. calcium phosphate D. uric acid stones E. magnesium ammonium phosphate stones from urea-splitting bacteria also called struvite stones F. Cystine stones in kids with hereditary cystinuria NEOPLASMS OF THE KIDNEY Benign 1. cortical adenomas 2. interstitial cells tumors (probably hamartomas) Malignant Two types of renal cell carcinoma 1. clear cell 2. papillary See slide 160/163: the first histo prep is the clear cell adenocarcinoma and the second is the papillary type. The third slide, ignore. Clear cell has rounded polygonal shapes with abundant, clear or granular cytoplasm. Papillary is full of foamy macrophages in papillae. General features (1) older persons (60 to 70 yo) (2) more in males (3) notorious for paraneoplastic endocrinopathies 19
  20. 20. (a) hypercalcemia (b) may cause nephrocalcinosis too Morphology • often multiple sites • most at poles of kidneys • invades renal vein • usu only one kidney affected See slide 159/163: kidney is split longitudinally, the white is the tumor, the red, the way the normal kidney looks. Clinical features (1) costovertebral pain (2) palpable mass (3) hematuria (4) bizarre growth patterns (a) silent for a long while (b) then explosive growth (5) however because of paraneoplastic state (a) polycythemia (from increased EPO) (b) hypercalcemia (from PTH) (c) hypertension (from ADH) (d) feminization (from estrogen) (e) Cushings syndrome (from ACTH) (6) metastasis to (a) lungs and liver (b) bone (c) brain (d) opposite kidney (7) late detection bc (a) no peritoneum, kidney is surrounded by a lot of fatswimming in perirenal fat, and minimal feeling with no compromise of renal function. Wilm's tumor (nephroblastoma) 1. common in kids under 10 2. 2nd most common tumor in kids 3. It’s a mix of primitive cells like a teratoma, it could be made up of: a. epithelium b. muscle c. bone d. cartilage 4. Could be due to a deletion of the short arm of chromosome #11 (sometimes trisomy) 5. Can be very massive tumors with distended abdomen (up to 30 lbs) 6. Usually unilateral 20
  21. 21. 7. Often see pulmonary metastasis but with chemotherapy and radiation has a 90% long term survival End:wk7PathMPart III.Sp06Roy 21

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