5 General Pathology Review & Introduction to Renal Pathology Flashcards Preview

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Flashcards in 5 General Pathology Review & Introduction to Renal Pathology Deck (21)
1

Homeostasis & the normal response of cells to physiologic stress

  • Homeostasis
    • Normal physiologic balance in the body
  • Normal response of cells to physiologic stress
    • Adapt
      • Hypertrophy (ex. muscles of body builders)
      • Atrophy (ex. leg muscles after paralysis
    • Necrosis
      • Cell death

2

Causes of cell injury & cell death

  • Causes
  • Reversible vs. irreversible cell injury
  • Cell injury
  • Necrotic cells

  • Causes
    • Oxygen deprivation
    • Ischemia
    • Physical agents (ex. radiation)
    • Chemical agents
    • Infections
    • Immunologic reactions
    • Genetic derangements
    • Nutritional imbalances
  • Reversible vs. irreversible cell injury
    • Reversible
      • Seen w/ EM but not microscope
      • Cellular swelling
      • Hydropic changes
    • Irreversible damage
      • Seen w/ EM & microscope
      • Coagulation of cytoplasmic proteins
      • Nuclear degeneration
  • Cell injury
    • Cell membranes are made of lipids
    • Influx of Ca --> decreased ATP, decreased phospholipids, disrupted proteins, & chromatin damage
    • Free radicals --> disrupted cell membranes, ribosome leakage, mitochondria problems, & lysosome rupture
    • Cell damage --> lubbimg membranes, swelling, & chromatin clumping
      • Normal cell --> recovery
      • Further injury --> more damage, more leakage, lysosome rupture --> digest cell contents
  • Necrotic cells
    • Eosinophilic due to increased binding of eosin (dye) to natured proteins (eosinophilia)
      • Increased red/pink cells from denatured proteins
    • Cytoplasm: glassy, homogeneous, & vacuolated (moth-eaten, due to digestion by lysosomal enzymes)
    • Focal, dystrophic calcification (low pH, high cytosolic Ca)

3

Different types of cell death

  • Necrosis
  • Other types

  • Necrosis
    • Coagulative
    • Liquefactive
    • Caseous
  • Other types
    • Autolysis
    • Apoptosis

4

Coagulative necrosis

  • Retains structure, loses function
  • Result of denaturing cellular proteins (coagulation)
    • Intracellular acidosis & Ca denatures cellular structural proteins & proteolytic enzymes --> blocks proteolysis
  • Basic outline of cells is preserved w/ nuclear degeneration
  • Occurs in hypoxia (decreased oxygen) & ischemia (decreased blood flow --> decreased oxygen)
  • Histology
    • Normal: lots of nuclei
    • Necrosis: destroyed nuclei, only see contours of cells
      • Glomeruli maintain structure longer than tubular epithelial cells

5

Liquefactive necrosis

  • Cells burst from fluid, lose structure
  • Seen in bacterial & fungal infections
  • Accumulation of inflammatory cells bring lytic enzymes (abscess)
    • --> complete digestion of dead cells
      • Via spillage of active lysosomal enzymes in injured cells or via inflammatory cells
    • --> liquid viscous mass (pus)
  • Histology
    • Top: abscess
      • Purple = nuclei of inflammatory cells release enzymes & cause necrosis
    • Bottom: lot of inflammatory cells & necrotic debris

6

Caseous necrosis

  • White & cheesy
  • Fragmented cells w/ coagulative necrosis & amorphous granular debris
  • Seen w/ mycobacterial infections or TB
  • Histology
    • Left: lung
      • Inflammatory cells on the outside
      • Homogenous stuff in the middle
      • Giant cells around it
    • Right
      • Looks like curd
      • Lots of proteins
      • Can barely make out the outline of any cells

7

Inflammation

  • General
  • Cellular response
  • Acute vs. chronic inflammation
  • When inflammation can be harmful
  • Repair

  • General
    • Essential for the body to defend itself against harmful agents (ex. bacterial infections)
    • Destroys injurious agents, dilutes injurious agents, & walls off the process
      • --> healing & reconstruction of the damaged tissues
  • Cellular response
    • Cells respond to chemotactic agents by exiting the blood stream into affected tissues & performing specific functions
  • Acute vs. chronic inflammation
    • Acute
      • Short lived (minutes to a few days)
      • Hallmark cell: neutrophil or granulocyte
    • Chronic
      • Longer duration
      • Hallmark cells: mononuclear lymphocytes, plasma cells, macrophages, & eosinophils
  • W/o inflammation
    • Infections go unchecked --> wounds never heal --> injured organs remain permanent sores
  • When inflammation can be harmful
    • Hypersensitivity rxns to insect bites or drugs
    • Rheumatoid arthritis when inflammation destroys joints
    • Atherosclerosis --> atheromas + decreased blood flow to organs
    • Glomerulonephritis --> renal failure
  • Repair
    • Resolution: regeneration of native parenchyma (ex. liver)
    • Organization: filling the defect w/ fibroblastic tissues or scar (ex. heart or muscles)
    • Most common: combination of both (ex. kidneys)

8

Inflammatory cells

  • In blood
    • Polymorphonuclear leukocytes (neutrophils)
    • Leukocytes
    • Platelets
    • Monocytes
    • Eosinophils
    • Basophils
  • In connective tissue
    • Fibroblasts
    • Macrophages
    • Macrophages & giant cells
    • Plasma cells
    • Mast cells
    • Proteoglycans, elastic fibers, & collagen fibers

  • In blood
    • Polymorphonuclear leukocytes (neutrophils)
      • Small
      • Multi-lobed nucleus never looks the same
      • Inflammatory granules
    • Leukocytes
      • Thin rim of cytoplasm
      • Perfectly round nucleus
    • Platelets
    • Monocytes
      • Phagocytic
      • --> macrophages when in connective tissue
    • Eosinophils
      • Bright red granules
      • Response to IgE mediated reactions or parasitic infections
    • Basophils
      • Larger granules
      • Darker blue
  • In connective tissue
    • Fibroblasts
      • Deposit collagen for repair
      • Chemotactic properties call in inflammatory cells
    • Macrophages
      • First cousin of monocytes
      • "Pac man," clean debris
    • Macrophages & giant cells
      • See granulomas
      • Engulf specific types of bacteria (ex. TB, leprosy, syphilis) or foreign bodies (ex. foreign body granulomas)
    • Plasma cells
      • Larger
      • Halo, clock face, eccentric nucleus (on one side of the cell)
      • Shouldn't be seen in the blood
      • Make immunoglobulins
      • First cousin of B lymphocytes
    • Mast cells
      • Release histamine to bring in fluid
      • Role in bee stings, etc.
    • Proteoglycans, elastic fibers, & collagen fibers
      • Repair

9

Granulomatous inflammation

  • aka type IV hypersensitivity rxn
  • Activated macrophages & multinucleate giant cells
  • Seen in...
    • TB
    • Sarcoidosis
    • Leprosy
    • Syphilis
    • Wegener's granulomatosis
    • Foreign body rxn

10

Renal pathology statistics

  • 20% of women get UTIs
    • Complications: acute & chronci pyelonephritis
  • 1% of ppl get renal stones
    • Complications: hydronephrosis, hydroureter
  • Dialysis & renal transplants keep pts alive
  • Many deaths related to renal diseases are in young pts

11

Gross pathology of the kidney

  • Normal kidney
  • Composition
  • Blood vessels --> ureter
  • Embryology: successive pairs

  • Normal kidney
    • Weight: 150 grams
    • Length: 12-15 cm
  • Composition
    • Cortex: 1.2-1.5 cm thick
    • Medulla: 12 pyramids + base at the corticomedullary junction
  • Blood vessels --> ureter
    • Blood vessels
    • --> 12 minor calyces
    • --> 2-3 major calyces
    • --> funnel shaped renal pelvis
    • --> ureter
  • Embryology: successive pairs
    • Pronephros
    • Mesonephros
    • Metanephros

12

Kidney problems

  • Congenital anomalies
    • Agenesis
    • Hypoplasia
    • Ectopic Kidneys
    • Horseshoe kidney
  • Cystic diseases
    • Congenital
      • Cystic renal dysplasia
      • Polycystic kidney disease
      • Medullary cystic disease
    • Acquired
    • Localized

  • Congenital anomalies
    • Agenesis: absence of kidneys
    • Hypoplasia: small & ill-formed kidneys
    • Ectopic kidneys: in the wrong place
    • Horseshoe kidney: 2 kidneys don't separate & are joined at the lower poles
  • Cystic diseases
    • Congenital
      • Cystic renal dysplasia: numerous small cysts in the kidneys, presents at a young age
      • Polycystic kidney disease: AR in childhood, AD in young adults
      • Medullary cystic disease: cysts mostly affect distal tubules in the medulla
    • Acquired
      • Associated w/ long-term renal dialysis
    • Localized
      • Simple
      • Vary in size
      • Commonly seen as incidental findings at resection or autopsy
      • Mostly asymptomatic

13

Renal biopsy

  • Purpose
  • Types
    • Closed core needle biopsy
    • Open biopsy
  • After biopsy
  • 3 portions
    • Largest
    • Small
    • Smallest

  • Purpose
    • Provide sufficient accurate info on which to base the right diagnosis, approach to treatment, & prognosis
  • Types
    • Closed core needle biopsy
      • Obtaiend by a tru-cut needle under ultrasound guidance & local anesthesia
    • Open biopsy
      • Perfomred in the OR under general anesthesia
  • After biopsy
    • Renal tissue is immediately submitted to pathology in normal saline for processing under a scanning microscope to ensure there's enough cortical tissue & >10-12 glomeruli
    • Complete study: light microscopy, special stains, IF microscopy, & EM
  • 3 portions
    • Largest: fixed in Bouin's fixative for 2 hours, washed, processed, & cut at 2-3 microns for light microscopy
    • Small: immediately frozen in OCT & cut at 5 micron thickness to be stained for Igs & studied under IF  microscopy
    • Smallest: cubed at 1mm & fixed in 2% glutaraldehyde sol'n, embedded in hard resin, cut, & examined under EM

14

Light microscopy: stains

  • H&E
  • Methamine silver
  • Periodic acid schiff (PAS)
  • Trichrome
  • Congo-red

  • H&E
    • Basic morphology
  • Methamine silver
    • Black
    • Basement membrane morphology (thickness, splitting, & spikes)
  • Periodic acid schiff (PAS)
    • Fuscia red
    • Basement membranes, deposits, & glycogen
  • Trichrome
    • Blue or green in a red background
    • Amt of fibrosis, chronicity of renal damage
  • Congo-red
    • Pink w/ apple-green birefringence under polarized light
    • Amyloidosis

15

Light microscopy: glomeruli

  • Cellularity
  • ECM
  • Peripheral capillary basement membrane
  • Bowman's space
  • Image: normocellular
  • Image: hypercellular
  • Image: mesangial sclerosis

  • Cellularity
    • Number of cells within mesangial areas, endothelial (intraglomerular vs. extraglomerular)
  • ECM
    • Sclerosis, increased mesangial sustance, fibrosis, amyloidosis, etc.
  • Peripheral capillary basement membrane
    • Thickening, wrinkling, splitting, etc.
  • Bowman's space
    • Normal or filled w/ hemorrhage, epithelial cells, proteinaceous substances, fat droplets, etc.
  • Image: normocellular
    • Tubules come togehter like a jigsaw puzzle
    • Can't see any interstitium
  • Image: hypercellular
    • Too many crowded cells
    • Increased cellularity --> not enough blood goes to the tubules --> tubules don't look good
  • Image: mesangial sclerosis
    • Diabetic kidney
    • Fibrotic nodules
    • Accentuated blood vessels & basement membranes

16

Light microscopy: tubules

  • Normal
  • Pathologic tubules
  • Pathologic tubular basement membranes
  • Pathologic lumen can be filled w/...
  • Image: normal
  • Image: blood
  • Image: luminal casts (hyaline)
  • Image: adenoma
  • Image: tubular necrosis
  • Image: tubular atrophy

  • Normal
    • Close together w/ little interstitial tissue
    • Open & empty lumen
  • Pathologic tubules
    • Necrotic (ex. acute tubular necrosis)
    • Degenerative (ex. atherosclerosis)
    • Dilated (ex. compensatory mech for lost adjacent tubules)
  • Pathologic tubular basement membranes
    • Thickened w/ amyloid deposits
    • Interrupted in severe injury
    • Wrinkled when tubular cells are necrotic
  • Pathologic lumen can be filled w/...
    • Proteinaceous material (ex. protein-losing syndromes)
    • Inflammatory cells (ex. pyelonephritis)
    • Blood (ex. glomerulonephritis)
    • Tubular casts
  • Image: normal
    • Tubules fit like a jigsaw puzzle around glomeruli
    • Tubules have enough nuclei around them & have a pearl color
  • Image: blood
    • Very bad to see RBCs in lumen
  • Image: luminal casts (hyaline)
    • Full of thick protein spilling --> renal failure
  • Image: adenoma
    • Abnormal proliferation or tubular epithelial cells
  • Image: tubular necrosis
    • Coagulative necrosis
    • See some outline of cells close to the membrane that will end up in the urine as casts
  • Image: tubular atrophy
    • Right: tubules look nice, fit together, & don't have space in b/n
    • Left: tubules are smaller, have thickened basement membranes due to cell loss, & expanded interstitium

17

Light microscopy: interstitium

  • Normal
  • Pathologic
  • Image: interstitial fibrosis
  • Image: interstitial inflammation

  • Normal
    • Framework that holds glomerular, tubular, & vascular structures together
    • Barely seen b/n tubules
  • Pathologic
    • Expand (ex. tubular atrophy)
    • Edema or inflammatory infiltrate (ex. pyelonephritis)
    • Fibrosis (ex. long standing chronic renal failure)
  • Image: interstitial fibrosis
    • Bad b/c see a lot of green interstitium b/n tubules
  • Image: interstitial inflammation
    • Red: eosinophils
    • Blue: plasma cells
    • See few tubules w/ many inflammatory cells

18

Light microscopy: blood vessels

  • Cellular changes
  • AffA & EffA
  • Interstitial arteries & arterioles
  • Image: normal
  • Image: mild intimal thickening
  • Image: severe fibroelastic intimal thickening / duplication of internal elastic lamina

  • Cellular changes
    • Intima, media, or adventitia
  • AffA & EffA
    • Thickness, fibrin, degeneration, etc.
  • Interstitial arteries & arterioles
    • Thickness, elastic lamina duplicaiton, inflammatoyr infiltrate, abnormal findings, etc.
  • Image: normal
    • Thin wall
    • Open lumen w/ RBCs & WBCs
  • Image: mild intimal thickening
    • Thickened intima
  • Image: severe fibroelastic intimal thickening / duplication of internal elastic lamina
    • Huge blood vessel w/ many elastic lamina
    • Intimal thickening or severe HTN

19

Immunofluorescence microscopy

  • Detects...
  • Procedure
  • Types of deposits
  • Locations

  • Detects...
    • Cellular changes in intima, media, adventitia, etc.
    • Ig, fibrin, or complement deposition within kidneys
  • Procedure
    • Multiple frozen sections are cut
    • Sections are stained by direct IF for...
      • Igs (IgG, IgM, IgA, Kappa & Lambda light chains)
      • Complements (C1q, C3, & C4)
      • Fibrinogen, transferrin, albumin, & alpha-2-macroglobulin
    • Positive & negative controls accompany studies
  • Types of deposits
    • Glomerular
    • Mesangial
    • Combined
  • Locations
    • Glomeruli
      • Linear vs. granular
        • Linear
          • Ex. antiglomerular BM antibody (anti-GBM)
          • Looks like cigarette smoke
          • Follows capillary walls
        • Granular
          • Ex. lupus
          • Little dots all over the place
          • Mesangial + capillaries
      • Subepithelial, subendothelial, or intramembranous
    • Tubules
      • BM, epithelial cells
    • Interstitium
    • Blood vessels (ex. thrombotic diseases)

20

Electron microscopy

  • Procedure: thick sections
  • Procedure: thin sections
  • Normal
  • Pathologic
  • Image: normal
  • Image: thick BM + electron dense deposits

  • Procedure: thick sections
    • Glutaraldehyde-fixed portion of cortex is embedded in plastic renin
    • Cut into 1-2 micron sections
    • Examined for the presence of glomeruli & tubules
  • Procedure: thin sections
    • Cut & stained for EM exam to detect abnormalities
  • Normal
    • Glomerular capillaries are patent
    • BMs are thin & intact
    • Epithelial cells show intact, sharp foot processes
  • Pathologic
    • Glomeruli have thick or interrupted capillary BMs & occasional deposits in subepithelial or subendothelial regions
    • Epithelial cells may lose foot processes
    • Mesangial cells may be increased in number & matrix deposition
      • Increased, duplicated, thinned, interrupted
    • Electron-dense deposits can be seen in mesangial areas
    • Bowman's space may have crescents or abnormal fat or proteinaceous droplets
  • Image: normal
    • In the glomerular capillary
      • Inside: blood
      • Outside: urine
    • See podocytes sticking off the outside
    • See fenestration on the inside
    • Filtratoin occurs in the BM
  • Image: thick BM + electron dense deposits
    • Thick, irregular, & filled w/ electron dense deposits

21

Glossary of descriptive terms

  • Diffuse
  • Focal
  • Segmental
  • Global
  • Sclerosis
  • Hyalinosis
  • Necrosis

  • Diffuse
    • All (>50%) of glomeruli are involved in the disease
  • Focal
    • Some (<50%) of glomeruli are involved in the disease
  • Segmental
    • Portion of teh glomerulus shows pathologic changes
  • Global
    • Entire glomerulus shows pathologic changes
  • Sclerosis
    • Fibrosis
    • Increased matrix (mesangial, in the vascular wall, increased fibrosis, etc.)
    • Loss of structure --> homogenous fibrosis, collagen deposition, etc.
  • Hyalinosis
    • Degeneration
    • Proteinaceous serum insudate (either glomerulus or arterioles)
  • Necrosis
    • Cell death