Path-kidney & diabetes exam Flashcards
Nephritic syndrome
- -visible hematuria (red cell casts)
- azotemia (↑ BUN & creatinine)
- mild to moderate proteinuria
- edema
- -hypertension
- oliguria
- Acute proliferative glomerulonephritis
- Poststreptococcal GN
- SLE
Nephrotic syndrome
- Heavy proteinuria ( > 3.5 gm/day)
- hypoalbuminemia ( <3 gm/day)
- hyperlipidemia
- LIPIDURIA
- generalize edema (severe)
NO → azotemia, blood, HTN, and more protein than nephritic
- membranous glomerulonephropathy
- minimal change disease
- focal segmental glomerulosclerosis
- MPGN I
Rapidly progressive (crescentic) glomerulonephritis
- Acute nephritis (signs of nephritic syndrome)
- proteinuria
- acute renal failure
- Crescents in most of glomeruli
- →parietal epithelial cells (line bowman’s) + monocytes & macrophages
Chronic renal failure
Progresses through 4 stages
–both kidneys become symmetrically smaller and granular
1) Diminished renal reserve– GFR 50% normal
- asymptomatic
2) Renal insufficiency– GFR 20-50% normal
- azotemia w/ anemia & HTN, polyuria, nocturia
3) Renal failure – GFR < 20-25% normal
- edema, acidosis, hypocalcemia, uremia may occur
4) End-stage renal disease– GFR <5% normal
- termal stage of Uremia
Uremia
Azotemia (↑ BUN & creatinine) + systemic manifestations
-waxy casts → not accute
- Dehydration
- Edema
- Metabolic acidosis → hyperkalemia
- Hypocalcemia → 2ry hyperparathyroidism
- Hyperphosphatemia
- renal osteodystrophy
- anemia → **burr cells/echinocytes (normo-cytic/-chromic)
- bleeding diatheses → nonthryombocyopenic purpura
- HTN or CHF
- fibrinous pericarditis
- Retinopathy
- hilar pneumonitis
- urine smell to breath
- pleural effusions
- GI (nausea, vomiting, bleeding,ulcers, bad taste, coated tongue)
- Neuromuscular (myopathy, neuropathy, encephalopathy
- Dermatologic (sallow color, pruritits, dermatitis)
Acute proliferative GN
–Poststreptococcal glomerulonephritis
Clinical presentation → **Nephritic syndrome (+ rash)
Pathogenesis → Immune complex mediated
-circulated or planted Ag
Morphology → enlarged, hyper cellular glomeruli, red cell casts in urine
Light Microscopy:
- diffuse ENDOcapillary proliferation
- → endothelial & mesangial cells
- leukocytic infiltration (PMN and monocytes)
Fluorescence Microscopy:
-Granular IgG and C3 → GBM and mesangium
Election microscopy → sub EPIthelial humps
Prognosis → excellent (better for child than adult)
-very low chance of → chronic GN
Rapidly progressive (crescentic) GN --Goodpasture syndrome
Clinical presentation: **Rapidly progressive GN (type I)
Pathogenesis: Anti-GBM COL4-A3 antigen
Light Microscopy:
- EXTRAcapillary proliferation w/ crescents & necrosis
- → proliferation of parietal cell
- → migration of monocytes macrophages
Fluorescence Microscopy:
-LINEAR IgG and C3; fibrin b/w cell layers crescents
Prognosis → poor
-Very strong chance → chronic GN
Chronic glomeruplonephritis
Clinical presentation: **Chronic renal failure
Pathogenesis: variable
Light Microscopy → Hyalinized glomeruli
Fluorescence Microscopy: granular or negative
Membranous glomerulonephritis
-Drugs, disease (HBV, HCV)
Clinical presentation: **Nephrotic syndrome
Pathogenesis → in-situ immune complex formation
- Ag mostly unknown
- 85% idiopathic
Light Microscopy
- early → normal
- late → diffuse, uniform thickening of capillary wall/BM
- silver stain → spikes of BM b/w deposits
Fluorescence Micro. → granular IgG & C3; diffuse
Election microscopy:
- irregular dense sub epithelial deposits
- **epithelial cell foot processes lost
Prognosis → good
- -poor response to steroids
- small/moderate chance → chronic GN
Minimal change disease (lipoid nephrosis)
Clinical presentation: **Nephrotic syndrome
-most frequent cause of NS in children
Pathogenesis → probably immune dysfunction
Light Micro. → normal; lipid in tubules
Fluorescence Micro. → negative
Election micro. → loss of foot processes
-NO deposits (vs. membranous w/ deposits)
Prognosis → Excellent
–good response to steroids
Focal segmental glomerulosclerosis
Clinical presentation: Nephrotic syndrome
-Non-nephrotic proteinuria
Pathogenesis
Light Micro. → focal and segmental sclerosis & hyaliniosis
- collapsed BM,
- ↑ mesangial matrix
- hyaline masses
Fluorescence micro → IgM and C3 in sclerotic region
Prognosis → poor
-responds poorly to steroids
–MPGN type I
Clinical presentation: Nephrotic/nephrotic syndrome
Pathogenesis → immune complex
Electron Microscopy → subendothelial deposits
Prognosis: good
–small/moderate chance → chronic GN
–Dense deposit disease (MPGN type II)
Clinical presentation: Hematuria chronic renal failure
Pathogenesis
Light Microscopy:
- mesangial & endocapillary proliferation
- GBM thickening
- splitting
Electron Microscopy → dense deposits
IgA nephropathy
Clinical presentation: Reccurent hematuria or proteinuria
-older children & young adults
Pathogenesis:
- IgA1 polymeric complexes trapped in mesangium →activate alt C’ → injury
- -genetic/acquired abnormality of immune regulation
- → ↑ IgA synthesis in response to respiratory or GI exposure to environmental agents (recurrent hematuria)
Light Microscopy:
- focal mesangial proliferative glomerulonephrtitis
- mesangial widening
Fluorescence Microscopy:
- prominant IgA in mesangium
- +/- IgG, IgM and C3 in mesangium
Electron Microscopy:
-mesangial & paramesangial dense deposits
Prognosis → Good
Alport
Hereditary GN
Clinical presentation: Hematuria
Pathogenesis → nerve deafness, eye disorders
Prognosis → poor
Thin basement membrane
Hereditary GN
Clinical presentation: Hematuria
Pathogenesis: Benign familial hematuira
Electron Microscopy → thin BM
Prognosis → excellent
Acute Tubular/Kidney Injury
- oliguria → uremia → recovery
- most common cause of acute renal failure
- Ischemic type → period of inadequate blood flow to peripheral organs, marked hypoTN, shock
- Nephrotoxic type → drugs, contrast agents, poisons
Morphology → skip lesions + casts
- Eosinophilic hyaline & Pigmented granular casts
- -distal tubules & collecting ducts
- -consist of Tamm-Horsfall protein → GP from cells of ascending think limb & distal tubules
- Epithelial regeneration
- -flattened epi cells w/ hyper chromatic nuclei & mitotic figures
Acute Pyelonephritis
-Acute suppurative inflammation of kidney due to bacterial infection (E. Coli, Proteus, Klebsiella)
- Sudden onset pain at CVA, fever
- dysuria, frequency, urgency
- urine → pyruia
- white cell casts → renal involvement
Morphology:
- patchy interstitial suppurative inflammation
- INTRAtubular aggregates of PMN
- tubular necrosis
Predisposing conditions:
- urinary / urinary tract obstruction
- pregnancy
- preexisting renal lesions
- vesicoureteral reflux
- diabetes
- immunosuppression & immunodeficiency
Chronic pyelonephritis morphology
due to **reflux nephropathy or chronic obstructive pyelonephritis
Gross:
- irregularly scarred (mountain & valleys)
- Hallmark → coarse, discrete, coritcomedullay scar overlying blunted, dilated calyx
- if B/L → involvement is asymmetric (vs chronic GN)
Micro:
- tubules → atrophy & hypertrophy
- dilated tubule may contain colloid casts (thyroidization)
- chronic interstitial inflammation & fibrosis → cortex & medulla
Acute drug-induced interstitial nephritis
-drug is happen → binds tubular cells → immunogenic → injury due to IgE and CMI
- Onset about **15 days after exposure to drug
- Fever, EOSINOPHILIA, rash, renal abnormalities
- -hematuria, mild proteinuria, leukocyturia (eosinophils)
Morphology:
- interstitial edema
- infiltration by lymphocytes & macrophages
- EOSINOPHILS and PMN
- may see granuloma
- varying tubular necrosis & regeneration
Analgesic Abuse Nephropathy
- Papillary necrosis first → cortical tubulointerstitial nephritis
- drug withdrawal → may stabilize or improve
- -otherwise → chronic renal failure
- transitional papillary carcinoma possible
- Acetaminophen → phenacetin → damages cell
- Aspirin → inhibits vasodilatory effects of PG
Gross:
- cortical atrophy overlying necrotic papillae
- -papillae at various stages of necrosis, calcification, fragmentation and sloughing
Micro → patchy/complete necrosis of papillae
-calcification
Causes of papillary necrosis
- Diabetes mellitus → several; all same stage of necrosis
- Analgesic nephropathy → all; different stages of necrosis
- Sickle-cell disease → few
- obstruction
Diabetes Criteria
1) HbA1c >= 6.5%
or
2) FPG >= 126 mg/dl after 8hrs fast (normal 70-100)
or
3) 2hr plasma glucose >= 200 mg/dl
(confirm all 3 by repeat test, esp. if acutely ill)
-Classic symptoms of hyperglycemia or hyperglycemic crisis, random plasma glucose >=200mg/L
Prediabetes criteria
- HbA1c 5.7-6.4%
- FPG= 100-125 mg/dL (normal 70-100)
- 2hr plasma glucose 140-199 mg/l
Type I Diabetes Mellitus
CLINICAL:
- Onset → childhood and adolescence
- normal weight/ weight loss preceding diagnosis
- progressive ↓ insulin levels
- circulating islet autoAb:
- -*anti-insulin
- -*anti-GAD (glutamic acid decarboxylase)
- -*anti-ICA512
- DKA in absence of insulin therapy
GENETICS:
- MHC II genes: HLA DR3/DR4
- CTLA4
- PTPN22
- insulin gene VNTR (variable number tandem repeats)
PATHOGENESIS:
-Dysfunction in T cell selection & regulation → loss self-tolerance to islet autoAg
PATHOLOGY:
- Insulitis → inflammatory infiltrate of T-cells & macrophages)
- β-cell depletion, islet atrophy
Type II Diabetes Mellitus
CLINICAL:
- Onset → usually adult
- vast majority obese
- ↑ insulin early → normal to ↓ insulin late
- no islet Ab
- Nonketotic hyperosmolar coma more common
GENETICS → diabetogenic & obesity-related genes
- TCF7L2
- PPARG
- FTO
PATHOGENESIS:
- Insulin resistance in peripheral tissues
- Failure of compensation by β cells
PATHOLOGY:
- No insulinitis; amyloid deposition in islets
- mild β-cell depletion
Adult polycystic kidney disease
Inheritance → autosomal dominant (always B/L kidney)
Pathologic features:
- asymptomatic until renal insufficiency at ~50
- large multicystic kidneys (B/L abdominal masses)
- liver cysts (40% polycystic liver disease)
- **berry aneurysms → stroke
- mitral valve prolapse → defect in BM
- PKD1 on chr 16 → polycystin 1
- PKD2 → disease at older age; later onset renal failure
Clinical features / complications
- *hematuria, proteinuria (<2gm/day), polyuria
- flank pain → hemorrhage, dilation
- renal colic from passage of clots
- *UTI, *renal stone
- *HTN
Typical outcome → chronic renal failure at 40-60ys
Childhood polycystic kidney disease
Inheritance → autosomal recessive (always B/L kidney)
Pathologic features:
-enlarged, cystic kidneys at birth
-PKHD1 on chr 6 → fibrocystin (cilium of tubular cells)
Perinatal & Neonatal:
- most common
- **Potter sequence at birth or rapid renal failure
Infantile & Juvenile:
- Assoc w. congenital hepatic fibrosis → portal HTN
- -↑ risk for cholangiocarcinoma
- liver disease predominates w/ ↑ age
Typical outcome → variable, death in infancy or childhood
Morphology → parallel cylindrical slit like cysts in cortex
-at right angles to cortical surface (whole tubule dilates)
Medullary sponge kidney
Inheritance → none
Pathologic features:
- multiple cystic dilations of **collecting ducts → medulla of adults
- discovered radiographically
- -incidental or related to complications →
Clinical features / complications:
- hematuria
- UTI
- recurrent renal stone (*calcifications in dilated ducts)
Typical outcome → benign
Morphology → dilated small cysts in medulla
- **cuboidal/ transitional cell lining
Familial juvenile nephronopthisis
Inheritance → autosomal recessive
-manifest in childhood or adolescence (most common)
Pathologic features: (medullary problem not nephron)
- corticomedullary cysts
- shrunken kidneys
- NPHP → nephrocystin (ciliary protein)
Clinical features / complications
- salt wasting, polyuria, nocturia (start wetting bed again)
- tubular acidosis
- UREMIA
- -azotemia
- -↓ Ca → hyperparathyroidism → demineralized bone
- -↑ phosohorus & K
Typical outcome → progressive renal failure beginning in childhood (most common genetic cause)
Morphology:
- cysts in the medulla at corticomedullary junction
- cortical tubular atrophy
- interstitial fibrosis
Multicystic renal dysplasia
Inheritance → sporadic (may be unilateral)
Pathologic features
- irregular kidneys w/ cysts of variable sizes
- enlarged, cystic kidney or flanks mass → at birth
Clinical features / complications
-assoc. w/ other renal abnormalities of lower UT
Morphology
- cartilage, undifferentiated mesenchyme
- immature collecting ductules
- abnormal lobular organization
Typical outcome:
- B/L → renal failure
- U/L → surgical cure
Morphology of benign nephrosclerosis
-Kidney of benign HTN, aging, DM
- Hyaline arteriolar sclerosis (pink and smudgy)
- kidney shrinks
- finely granular cortical surface
Unilateral renal artery stenosis
-Atherosclerosis causes most
- Fibromuscular dysplasia also causes
- -younger women
- -fibrous, elastic tissue or muscular thickening of vessel wall
- -→ beaded appearance on X-ray
→ causes renal vascular hypertension in C/L kidney
–hyaline arteriolar sclerosis
Ischemic Kidney:
- small, shrunken
- tubular atrophy
- interstitial fibrosis w/ inflammatory cells
- ↓ urine output
- ↑ renin in renal bein
Normal Kidney:
arteriolar sclerosis
Diffuse cortical necrosis
-associated w/ shock & obstetrical accidents
Renal Stone types
Calcium Oxalate & Phosphate (70% of stones)
- small cube/diamond shape
- acidic urine
- hypercalciuria w/o hypercalcemia (idiopathic)
- ↑ GI calcium absorption or impaired reabsorption
- radio-opaque
- Oxalate crystals → ethelyene glycol
Magnesium Ammonium Phosphate (5-10%)
- alkaline urine
- assoc. w/ infection Proteus
- Staghorn calculi → take shape of calyces & pelvis
- look like bars of gold
- radio-opaque
Uric Acid (5-10%)
- rectangular, longer (parallelogram)
- football/star shap
- acidic urine
- gout
- leukemia, lymphoma- tumor lysis syndrome
- radiolucent
Cystine (1-2%)
- only hexagon shaped
- hereditary causes
- acidic urine
Hyaline granular casts →
Renal tubular epithelial casts →
Waxy cast →
Leukocyte cast →
RBC cast →
Oval fat bodies/ fatty cast →
Broad waxy cast →
Hyaline granular casts → acute tubular injury
Renal tubular epithelial casts → acute tubular injury
Waxy cast → tubules atrophic (not acute)
Leukocyte cast → pyelonephritis
RBC cast → bleeding from glomerulus
Oval fat bodies/ fatty cast → always nephrotic
Broad waxy cast → caput end stage kidney
Benign renal neoplasms
- Renal “adenoma”
- oncocytoma → intercalated cells of collecting ducts
- angiomyolipoma → perivascular epithelioid cel
- -tuberous sclerois
Malignant renal neoplasms
- conventional renal cell carcinoma (clear cell)
- -→ renal tubular or collecting duct epithelial cell
- -papillary
- -chromophobe
- -translocation
- -collecting duct
- Urothelial (transitional) cell carcinoma of calyces/pelvis
- Wilms tumor (nephroblastoma) → stem cells
Bladder cancer risk factors
1) cigarettes
2) aromatic amines or aniline dyes
3) schistosoma haematobium (squamous carcinoma)
present w/ painless hematuria and maybe obstruction
Cause of diabetic vascular disease
Chronic hyperglycemia →
1) AGE → RAGE (T cell, macrophage, endo, vascular SM)
- Large vessels:
- -crosslink type I collagen → ↓ elasticity
- -crosslink & traps plasma & matrix proteins
- -traps LDL in atheroma
- Small vessels
- -binds type IV collagen of BM → crosslinks w/ albumin
- → microangiopathy
2) Activated PKC
- ↑ VEGF → diabetic retinopathy
- ↑ TGFβ
- ↑ PAI-1 → procoagulation
Cause of diabetic nerve & lens damage
↑ intracellular glucose in nerve/lens → sorbitol → fructose
- -via aldose reductase
- -uses up NADPH → ↓ antioxidant GSH
- ↑ susceptibility to oxidative stress
conditions w/ elevated PSA
- prostate carcinoma
- BPH
- Prostatitis
- infarct
- instrumentation
Cadmium
-pulmonary toxicity → obstructive lung disease
Nephrotoxicity
- concentrates in proximal convoluted tubules
- acute toxicity → proteinuria
- chronic toxicity → hypercalciuria, osteopenia, gractures
- -prostate & renal cancer risk
