3 penyakit tubulus dan interstitium_a

8/12/2019 3 Penyakit Tubulus Dan Interstitium_a

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Diseases Affecting Tubules and

Interstitium


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Tubulointerstitial Nephritis

Glomerulus is spared Divided into Infectious and Non-infectious Infectious

Bacterial infection - Pyelonephritis Usually due to E. coli

Affects the renal pelvis first hence Pyelo

Non-Infectious - Interstitial Nephritis


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Tubulointerstitial Nephritis

Interstitial Nephritis - Not Infectious Drugs Metabolic injury

hypokalemia

Radiation injury

Immunologic mechanisms


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Acute Pyelonephritis

Though Pyelonephritis is almost alwaysassociated with an infection of the lowerurinary tract

There are many more bladder infections thatdont lead to pyelonephritis


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Pathogenesis

E. coli and other gram negative rods Proteus, Klebsiella, Enterobacter and

Pseudomonas

UTI think E. coli


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Pathogenesis Ascending infection is the most important

route by which bacteria reach the kidney Almost all UTIs are from ascending infection

Urethral colonization is the usual first step

Instrumentation (catheterization,cystoscopy, etc)


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AcutePyelonephritis


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Pathogenesis Can result from hematogenous spread

Think Infective Endocarditis Other causes of septicemia


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Pathogenesis In the absence of instrumentation, UTI most

commonly affects females Trauma to the urethra during sexual intercourse

and the shortness of the urethra allow bacterialentry


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Pathogenesis Normal bladder urine is sterile

Periodic voiding

Antimicrobial properties bladder mucosa

Outflow obstruction - Prostate hypertrophy Bladder dysfunction - Paraplegia Lead to increased UTIs


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Vesicoureteral Reflux

Obstruction is critical to the development ofUTI

But, incompetence of the vesicoureteral junction allows the bacteria to ascend

Normal ureteral insertion allows one wayflow

Incompetent valves allow vesicoureteralreflux (VUR)


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Still, the obstruction (e.g. due to ProstateHypertrophy) will overcome even a

competent vesicoureteral junction


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Predisposing factors for development ofUTI Obstruction VUR Pregnancy

Instrumentation of urinary tract Diabetes Mellitus


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Diabetes Mellitus and UTI

DM increases the risk of SeriousComplications of UTI Pyelonephritis Septicemia Necrotizing Papillitis

Recurrent UTIs


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Morphology of Pyelonephritis

Gross Discrete yellowish raised abscesses on the renal

surface (fig 14-14, p 456) Microscopic

Abscess formation


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Pyonephrosis

Obstruction with Pyelonephritis leading to A Pus - bag, Ureter, calyces and pelvis

filled with pus YUCCHHH!


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Papillary tip necrosis or

necrotizing papillitis Think Diabetes!!! Otherwise this is

thankfully rare

The papillary tips (the tips of the renalmedullary pyramids) undergo ischemicnecrosis

It says it is a combination of suppurative andischemic but it is ischemic necrosis alone!!!


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Papillary Tip Necrosis or Necrotizing Papillitis

Blue Arrow = Papillary Tip Necrosis

Yellow Arrow = Sloughed Papillary Tip


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Clinical Sudden onset of:

Flank pain

Chills, Fever and Malaise Dysuria, Urgency & Frequent Urination Urine shows

Pyuria Bacteriuria WBC CASTS


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Papillary Tip Necrosis

Clinical Usually this is a clinically silent entity

The book states that key signs are sepsis and

renal failure Actually, sepsis and renal failure are very rare


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Papillary Tip Necrosis

Clinical The usual lab finding is modest proteinuria

Less than nephrotic range (


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Chronic Pyelonephritis and

Reflux Nephropathy Interstitial Inflammation associated with

scarring of the calyceal-pelvic area

Two forms Chronic Obstructive Reflux Nephropathy


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Chronic Obstructive

Pyelonephritis Obstruction leads to recurrent bacterial

infections

Leading to chronic inflammation, tubulardestruction and scarring

IF THE OBSTRUCTIVE LESIONS AREBILATERAL!!!!! e.g. posterior urethralvalves can lead to chronic renal failure


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How can Obstruction lead to

infection??? Obstruction is not complete It is relative obstruction or better said,

partial obstruction Common medical usage is Obstruction

when we mean intermittent or partialobstruction


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Reflux Nephropathy

Again, the common theme is recurrent bacterial infections.

This time on top of Vesico-Ureteral Reflux(VUR)

This is more common than the Obstructiveform


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Chronic Pyelonephritis

Morphology - Gross HALLMARK is scarring of the kidney from

the renal calyx or pelvic area out to the

surface of the kidney Uneven, asymetric renal scarring between

the two kidneys


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Morphology - Micro HALLMARK is thyroidization

Dilatation of tubules with atrophy of lining

epithelium Pink, glassy casts, so- called colloid casts These changes give a thyroid-like appearance

Inflammation and scarring of calyx Inflammatory infiltrate is overwhelmingly

CHRONIC , i.e. lymphocytes & Plasma Cells


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Clinical Course Gradual onset of renal insufficiency New onset of Hypertension IVP (intravenous pyelogram)

Shows blunted calyces Asymmetric scarring


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Clinical Course Polyuria and nocturia Loss of concentrating ability

Cant put out the Sodium

Glomerular lesions do occur


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Board Question What Glomerular lesion is associated with


Focal Segmental Glomerulosclerosis Clinically -Nephrotic Syndrome


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Drug-Induced Interstitial

Nephritis Think Antibiotics and Analgesics Acute and Chronic Forms


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Acute Drug-Induced Interstitial

Nephritis Methicillin, Ampicillin (synthetic

penicillins)

Rifampin (anti-TB drug) Nonsteroidal anti-inflammatory drugs

(NSAIDS)

Diuretics (thiazides)


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Acute Drug-Induced Interstitial

Nephritis Onset 2 weeks after exposure to drug

May happen after ingestion of the first pill

Fever, transient skin rash, eosinophilia Hematuria, mild proteinuria, eosinophiluria Acute Renal Failure in 40-50%

Walkers Law : -)

Withdrawal of offending drug almostalways leads to recovery


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Acute Drug-Induced Interstitial Nephritis

Morphology Interstitial Inflammation

Lymphocytes, plasma cells

Eosinophils and neutrophils may be present Tubulitis Granulomatous inflammation may occur Associated minimal change disease with

nephrotic syndrome also happens


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Figure 14-16 p 459


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Acute Drug-Induced Interstitial Nephritis

Pathogenesis

Immune mechanism Type I and/or Type IV

Drug acts as hapten binding to someunknown cytoplasmic or ECM component

The combination is immunogenic Leading to Type I +/or Type IV reaction


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Analgesic Nephropathy

Unlike Acute drug-induced interstitialnephritis which may occur after ingestion of

the first pill Analgesic Nephropathy only occurs after

ingestion of large quantities of analgesics

over a long period of time The implicated analgesics are usually some

combination of phenacetin, aspirin, acetaminophen,caffeine and/or codeine


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Pathogenesis Acetaminophen, a metabolite of phenacetin

causes injury by covalent binding and

oxidative damage Aspirin inhibits prostaglandin synthesis

Predisposes papilla to ischemic injury


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Morphology Chronic Interstitial Nephritis Papillary tip necrosis

Pyelonephritis Diabetics Analgesic Nephropathy


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Clinical Course Chronic renal failure Hypertension Anemia INCREASED RISK of TRANSITIONAL

CELL CARCI NOMA of the RENAL PELVIS


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Acute Tubular Necrosis (ATN)

Tubular necrosis is very subtle in acutetubular necrosis

Destruction of tubular epithelial cells wayoverstates what is seen

Clinically, acute renal failure

ATN is the most common cause of AcuteRenal Failure


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Acute Renal Failure

A rapid decline in renal function usuallyoccurring over 24 hours to several days as

measured by Rise in Blood Urea Nitrogen (BUN) and

Plasma Creatinine

Oliguria (decreased urine output to less than400 ml urine/24h)


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Acute Renal Failure

Causes Pre-Renal Renal Post Renal

THIS IS NOT IN YOUR BOOK BUT ISVERY IMPORTANT!!!!!!!!!!!!!!!!!!!!!!!


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Acute Renal Failure

Pre-Renal Relative decrease in blood volume

CONGESTIVE HEART FAILURE

Sepsis Others


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Acute Renal Failure

Pre-Renal Absolute decrease in blood volume

Hemorrhage

Severe burns Diarrhea Diuretics


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Acute Renal Failure

Renal Glomerular

Acute glomerulonephritis

Crescentic glomerulonephritis Tubules

Acute interstitial nephritis

Acute tubular necrosis Vascular

Vasculitis


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Acute Renal Failure

Post-Renal Obstruction

Bladder outlet obstruction

Nodular hyperplasia of the prostate Ureteral Obstruction

Must be bilateral thus this is RARE


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Acute Tubular Necrosis

Ischemia or Toxins Hypotension secondary to

Shock

Sepsis Trauma Pancreatitis

Rhabdomyolysis Hemolysis


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Ischemia or Toxins Drugs

Aminoglycosides

Other antibiotics Radiocontrast agents Heavy metals (e.g. mercury) Organic solvents (e.g. carbon tetrachloride)


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Pathogenesis Critical events are

Tubular injury

Altered blood flow


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Pathogenesis - Tubular Injury The tubular epithelium is very sensitive to

ischemia

High number of mitochondria used to powerthe active metabolic needs of the tubule

Tubular functions predispose to injury

Large surface area for reabsorption Active transport of ions and organic acids Active concentration of resorbed material


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Pathogenesis - Hemodynamics Vasoconstriction decreases GFR Switch from cortical to medullary blood

flow


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Morphology Individual cell necrosis occurs Injured epithelial cells slough into the

lumen of the tubule Remaining cells flatten to cover the

basement membrane

Tubular dilatation occurs


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Morphology

Very difficult to tell ischemic from toxic

forms of ATN Except in animal models


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Clinical Course Initiating , Maintenance, Recovery Initiating Phase

Onset 36 h-6d & dominated by inciting event Surgery, OB, Medical event

Mild Increase in BUN, Creatinine

Mild decrease in urine output NOT OLIGURIA


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Clinical Course Initiating, Maintenance , Recovery Maintenance Phase

Onset 2-6d with Oliguria 50-400 ml/day urine ANURIA is rare

Rapidly rising BUN, Creatinine

Signs and symptoms of Uremia & FluidOverload

Can last up to 3-6 weeks


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Clinical Course Initiating, Maintenance, Recovery Recovery Phase

Steadily increasing urine volume 3-6 liters/day Bad urine because filtration has returned but

tubules dont work

Electrolyte imbalance and hypovolemia Subtle tubular dysfunction persists for months Eventually complete recovery


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Mortality Mortality remains at about 50% This in spite of dialysis and good supportive

care There has been no change in mortality since

the introduction of dialysis during the

Korean War


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Benign Nephrosclerosis

Renal changes seen in Diabetes

Benign Hypertension Morphology

Gross

Small, diffusely and finely granular Microscopic

Arteriolar Hyalinosis

Arteriolar H alinosis


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Hyaline = Pink and Shiny Hyaline material accumulates causing

Decreased blood flow Results in ischemic atrophy

Patients with this usually die of other

complications of diabetes or hypertension


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Malignant Hypertension

Malignant Nephrosclerosis Much less common that Benign

hypertension

Pathogenesis is unclear


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Malignant Nephrosclerosis There is increased permeability of small

vessels Leak fibrinogen, plasma proteins, platelets Hence, fibrin oid necrosis of arterioles Intravascular thrombosis

Mitogenic factors lead to Endothelial Proliferation

Onion Skinning


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Malignant Nephrosclerosis Occlusion of afferent arterioles

Marked stimulation of renin-angiotensis system Bad Hypertension Aldosterone increased Renin increased


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Malignant Nephrosclerosis Morphology

Fibrinoid necrosis Platelet fibrin thrombi Endothelial proliferation

Correct Pathologic name is

Thrombotic Microangiopathy


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Thrombotic Microangiopathy


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Malignant Nephrosclerosis

Clinical Course Diastolic blood pressure >120 mm Hg Evidence of end-organ damage

Papilledema

Encephalopathy Cor abnormalities Renal failure


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Clinical Course Related to Increased intracranial pressure

Headache Nausea

Vomiting Scotomas (area of lost vision)


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Clinical Course Proteinuria & Hematuria Acute Renal Failure Only 50% survive 5 years


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Other Causes of Thrombotic

Microangiopathy Histologically indistinguishable from the

lesions seen in malignant hypertension Hemolytic uremic syndrome (HUS)

Childhood form associated with verotoxin

producing E. coli usually in hamburgers Thrombotic thrombocytopenic purpura

(TTP)


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Cystic Diseases of the Kidneys

Simple Cysts

Autosomal Dominant Polycystic KidneyDisease (APKD) Autosomal Recessive Polycystic Kidney

Disease (APKD)


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Simple Cysts Benign fluid filled cyst lined by cuboidal

epithelium and filled with clear fluid 1-5 cm in diameter Main importance is distinguishing these from

renal cell carcinoma


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Autosomal Dominant Polycystic KidneyDisease (APKD)

ADULTS Multiple expanding cysts in BOTH kidneys Ultimately destroying them


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Autosomal Dominant Polycystic

Kidney Disease Genetics

1 in 1000 have APKD

10% of all cases of Chronic Renal Failure 85-90% of cases have a defect in polycystin 1

Located on the short arm of chromosome 16

Polycystin 1 is a cell membrane associated protein which is largely extracellular How a defect in this protein leads to cysts is

UNKNOWN


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Kidney Disease

Morphology - Gross Kidneys become enormous 4 kg each Look like a mass of cysts


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Kidney Disease

Morphology - Microscopic A little normal kidney between huge cysts lined

by flattened epithelium Cyst fluid is either clear, yellow or hemorrhagic



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Autosomal Dominant PolycysticKidney Disease

Clinical Course USUALLY NO SYMPTOMS TILL 4TH OR 5TH

DECADE Flank pain Abdominal pain

Gross hematuria



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Clinical Course Complications

Hypertension Urinary tract infections Berry aneurysms of the Circle of Willis in 15-20%

Walkers Law : -)

Liver cysts (usually asymptomatic) in 30% Walkers Law FAILS : -(



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Clinical Course

Prognosis Slowly progressive to end-stage renal disease atabout age 50

Autosomal Recessive Polycystic


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Autosomal Recessive PolycysticKidney Disease

Childhood

Rare Usually manifests at birth Death early from renal failure

Autosomal Recessive Polycystic


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Autosomal Recessive PolycysticKidney Disease

Numerous small cysts leading to renalenlargement

Sponge-like appearance Associated with liver and bile duct cysts in

almost all cases If survive infancy, develop cirrhosis

3 penyakit tubulus dan interstitium_a

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