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Vijesh Pate

Renal Pathology III

Diseases affecting the tubules and interstitium usually both are affected together not individually, hence tubule-interstitial disorders

- No nephritic or nephrotic syndrome present- InsteadProblem w/ tubular function

o Concentration ability leading to polyuria, nocturia, salt wasting, disturbance acid secretion (metabolic acidosis)o ARF: abrupt suppression of renal function leading to s/s ofazotemia & uremia w/in weeks

Oliguria: less than 400 ml / day of urine Anuria: less than 100 ml / day of urine

Classifications: 1) Pre-renal: starts before the kidney (thrombosis of renal artery)o 2) Intra-renal: disease starts at the kidney (RPGN, other renal disease)o 3) Post-renal: starts after the kidney (obstruction, stone, etc.)

**Most common cause = Acute tubular necrosis (ATN) / Acute kidney injury (AKI)Epi Pathogenesis / Antibodies S/S *

ATN Death of the tubular epithelium

cells = loss of function

Reversible

Loss of polarity = Na/K ATPase @

apical instead of the basolateral

side = Na lossMacula densa

osmotically swell afferent

arteriole constriction GFR

Detachment of epithelial cells =

formation of casts in the urine =

GFR

Irreversible Ischemia b/c of loss of blood =

adrenergic response, leading to

afferent arteriole constriction =

flow to efferent arteriole =

necrosis and apoptosis of the cells

= tubular flow

ALL result in OLIGURIA

Early management can be

reversed

- Initiation phase: swollen kidneys

urine output + BUN

- Maintenance phase: urine

output at lowest point, electrolyte

imbalance, K, uremia

Need dialysis to survive

- Recovery phase: regenerationoccurs, maturation of the tubular

cells, polyuria (b/c immature cells

leak), K

- Better prognosis w/ toxic

Ischemia blood supply (Hypotension,

shock, hypovolemia [diarrhea,

bleeding])

Multiple points w/ SKIPS

History: recent hemorrhage,

hypotension, surgery

Urinalysis: muddy (dirty) brown

urine b/c of many cytochrome

pigments

Coagulative necrosis: cells

appear eosinophillic (pink) w/ no

nuclei

o Regeneration = flattened cellsbut not truly functional (ie. leaky

edema)

Toxins Exogenous: nephrotoxins

Antibiotics (aminoglycosides,

amphotericin B)

Radiographic agents, heavy

metals, organic solvents

(ethyelene glycol @ brake fluids /

anti-freeze)

Endogenous: proteins

Myoglobulins: massive trauma

(crush) = enter blood

Hemoglobulins: excessive

hemolysis (wrong blood type =

HSR) = overload of hemoglobins

Mostly PT w/ NO SKIPS

spares the distal tubule and BM

Mercury: damaged cells have

acidophilic inclusions

CCl4: accumulation of lipids with

necrosis

Ethylene glycol (antifreeze /

brake fluid): metabolized in the

liver by ADH = Oxalic acid + Ca =

Calcium oxylate crystals

Ballooning degeneration +

vacuolization

Tubulo-interstitial nephritis

Acute PN More in young women (15-40)

- 1) Shorter ureter

- 2) No anti-bacterial protection

(ie. Prostatic fluid)

- 3) Progesterone :. Common

during child bearing age

Mostly gram negative bacilli

(E.coli, proteus, klebsiella)

Affects tubules, interstitium &

renal pelvis

2 routes:

- Hematogenous route (staph)

- Ascending infection

From lower urinay tract

Vesico-ureteral reflux

- PROGESTERONE = flaccid, loss of

oblique course b/c of congenital or

many infections

Intra-renal reflux

- Upper + lower poles have

indentations (round papillae) that

allow for stagnationallow

bacterial growth

N infiltrate of interstitium &

tubules

- Abscesses: @ upper/ lower poles

Costovertebral angle tenderness

Fever, chills, N&V, dysuria,

freq.

Bacteriuria, WBC (pyuria), WBC

casts

Complications:

- Pyonephritis: pus in renal pelvis

- Papillary necrosis: destroy small

tubular capillaries in medulla

(Also w/ sickle cell, renal TB,

diabetes)

Chronic PN Scarring + flattening of calyces Corticomedullary scar over a

blunted, dilated, deformed calyx

Lymphocytes + plasma cell

infiltrate

Thyroidization colloid casts in

tubules

Reflux type Most common VU reflux beginning in childhood * Only pole calycies affected

Obstructive type Progress from acute PN Obstruction of lower urinary tract

- Cause:

Large scarred areas + distortion

of pyramids (Papillary necrosis)

Gradual onset renal insufficiency

HTN

Proteinuria b/c of FSGS + end

stage renal failure

* All calycies affected

DDX: CGN

- this is asymmetric

Xanthogranulomatous PN Ass w/ proteus infections Accumulation of foamy M and

giant cells

Large yellow nodules DDX: NOT renal carcinoma

- Yellow nodules occur here too

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Vijesh PateEpi Pathogenesis / Antibodies S/S *

Acute drug induced

tubulointerstitial nephritis

(Hypersensitivity nephritis)

15 days after drug exposure

(Methicillin, Ampicillin,

sulphonamides, NSAIDS)

Drugs act as hapten

Type 1 HSR = Eosinophillia

Type 4 HSR = Granulomas

Azotemia, oliguria, fever,

eosinophilia, rash, proteinuria

(mild), hematuria

Papillary necrosis

Renal failure in 50% of pxns

Analgesic abuse nephropathy Analgesic mixtures = chronic TI

nephritis + renal papillary necrosis

Analgesic abuse

- Phenacetin Acetaminophen

(free radical damage)

- Aspirin inhibits prostaglandinleading to vasoC of afferent art. =

Papillary necrosis followed by TI

nephritis

All papillae are affected

- Different stages of necrosis

- DDX: Diabetes = same stage

Dystrophic calcification, sloughing

Long term complication

- Transitional cell carcinoma of

renal pelvis / ureter / bladder

**Papillary Necrosis**

1) Acute tubulo-interstitial nephritis, 2) Analgesic nephropathy, 3) Diabetes, 4) Sickle cell anemia or trait, 5) Renal TB, 6) Urinary tract obstr uction

**NSAID associated nephropathy**

1) Acute hypersensitivity Tubulo-interstitial nephritis, 2) Lipoid nephrosis (MCD), 3) Membranous GN

Urate nephropathy Uric acid crystals

w/ adjacent fibrosis + atrophy of

renal parenchyma

Acute uric acid nephropathy Chemotherapy leading to tumor

lysis syndrome

- ARF b/c of uric acid

Chronic uric acid nephropathy Gout tophi

- Moonshine for gouty attack

precipitating in tubules

- Tophi present causes a fibrosing

reaction (via fibroblasts)

Nephrolithiasis Uric acid stones

Multiple myeloma Plasma cell cancer = light chains

- Bence jones + Tamm horsfall

proteins Complexes

- Obstruct tubular lumen =

granulomatous inflammation

- Multinucleate giant cells present

Amyloidosis

Hypercalcemia & Hyperuricemia

**Urinalysis in ARF**

ATN = dirty brown casts + epithelial cells

AGN = RBC casts + proteinuria

Acute TI nephritis = WBC casts + pyuria (pus)

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Vijesh PateEpi Pathogenesis / Antibodies S/S *

Kidney complications that can result as a complication to HTN

Benign nephrosclerosis

(Hyaline arteriosclerosis)

HTN (moderate) - Medial + intimal thickening

- Hyaline deposition b/c proteins

are pushed out

Sclerosis of renal arterioles + small

arteries

GFR + mild proteinuria

Shrunken kidney

- Surface is fine granular

Malignant nephrosclerosis Malignant HTN

History of MI, stroke, papilledema

- permeability to proteins

- Endothelial injury

- Platelet deposition GF release

leads to hyperplastic arteriolitis

Onion skin appearance

- Fibrinoid necrosis + thrombosis

NECROTIZING ARTERIOLITIS

Flea bitten kidney

- Rupture of capillaries = petechial

hemorrhages

mortality

Renal artery stenosis (RAS) HTN caused by RAS activity in

the ischemic kidney

- renin

** Important b/c this can be

surgically cured

DDX: Hyperaldosteronism (Cohns

syndrome) renin

1. Occlusion by atheromatous

plaque

Older males

2. Fibromuscular hyperplasia Younger females Smooth muscle hyperplasia

(media)

- blood flow to kidney

Angiogram = beading effect

- Multiple constrictions

Trichrome stain = thickening of

media

Thrombotic microangiopathies

HUS / TTP Syndrome

Thrombosis of capillaries and

arterioles throughout the body

MAHA

Thrombocytopenia

Renal failure

1. Hemolytic uremic syndrome E.coli infectin (Type O157:H7)

- Infected meat

Renal symptoms mostly

- Diarrhea, MAHA- Oliguria, hematuria, HTN, ARF

Blood smear schistocytes

Kidney cortical necrosisArterioles fibrinoid necrosis +

subENDOthelial fibrin deposits

2. Thrombotic thrombocytopenic

purpura

CNS symptoms mostly

Diffuse cortical necrosis **Occurs in conditions w/ DIC

- Abruptio placentae, HUS, septic

shock

Bilateral + symmetrical cortical

necrosis

- columns of berteni are affected

- medulla is unaffected

- smallest vessels are in the cortex

Pale changes to cortex

Renal infarctions **Develops b/c ofthromboemboli

or vegetations on the left heart

- Results of atrial fib

- Flank pain, fever, leukocytosis

- Proteinuria, hematuria

Pale wedged shaped lesions

- Coagulative necrosis (no nuclei)

Obstructive uropathy

(Hydronephrosis)

Male

BPH

Female

pregnancy (ureter pressed)

uterine prolapse (cystocele)

Both stones (urinary calculi)

Obstruction of the urine outflow

- Leads to dilation of renal pelvis &

calyces

- Atrophy of the kidney

Stagnation of urine = risk ofinfection & stone formation

Permanent damage if:

- Partial obstruction for 3 mths

- Complete obstruction for 3 wks

Intravenous pyelogram shows:

- dilation of renal pelvis + calyces

Cortical thinning