Renal Flashcards Preview

Pathology > Renal > Flashcards

Flashcards in Renal Deck (144)
Loading flashcards...
0

How are glomerular diseases mediated and how are tubular/interstitial diseases mediated?

Glomerular = immunologically mediated

Tubular/interstitial = toxic or infectious agents

1

Azotemia

↑ BUN and creatinine levels with ↓ GFR

2

Prerenal and postrenal azotemia

Prerenal = hypoperfusion of kidneys impairing renal function without parenchymal damage.

Postrenal = obstructed urine flow beyond level of kidney

3

Uremia and secondary manifestations

failure of renal excretory function, metabolic and endocrine alterations from renal damage.

secondary manifestations in: GI system, peripheral nerves, heart

4

Nephritic Syndrome

from glomerular disease.

from inflammation in glomeruli.

features: acute onset, hematuria, mild to mod proteinuria, HTN, red cell casts in urine, azotemia, oliguria.

classically: acute poststreptococcal glomerulonephritis

5

Rapidly progressive glomerulonephritis

nephritic syndrome with rapid decline in GFR.

6

Nephrotic Syndrome

  • from glomerular disease.
  • deranged capillary wall ⇒ ↑ permeability to plasma proteins (↑ proteinuria) ⇒ hypoalbuminemia and reversed albumin:globulin ratio.
  • ↓ colloid osmotic pressure and Na/water retention ⇒ edema
    • most markedly in periorbital regions.  also ascites and pleural effusions.
  • hypogammaglobulinemia ⇒ ↑ risk infection.
  • hypercoagulable state - from loss of antithrombin III.
  • ↑ synthesis lipoproteins in liver, abnormal transport of circulating lipid particles, and ↓ catabolism ⇒ hyperlipidemia and hypercholesterolemia may ⇒ fatty casts in urine, oval fat bodies or free fat in urine.
  • in kids: primary kidney lesion ⇒ minimal change disease, membranous GN (older adults), and FSGS (all ages).
  • in adults: from systemic diseases = SLE, diabetes, amyloidosis
  • features: heavy proteinuria (>3.5gm/day), hypoalbuminemia, severe generalized edema, hyperlipidemia, lipiduria, hypogammaglobulinemia

7

Asymptomatic Hematuria/Proteinuria

manifestation of subtle or mild glomerular abnormalities.

8

Acute Renal Failure

features: oliguria or anuria, recent onset azotemia from glomerular, interstitial, or vascular injury or acute tubular injury. frequently reversible.

9

Chronic Renal Failure

prolonged signs and symptoms of uremia. is end result of all chronic renal parenchymal diseases.

major cause of death from renal disease.

10

Renal Tubular Defects

features: polyuria, nocturia, electrolyte disorders (metabolic acidosis).

from direct effect on tubular structure or from defects in tubular functions (can be inherited or acquired).

11

UTI

features: bacteriuria and pyuria.

symptomatic or asymptomatic.

may affect kidney or bladder

12

Nephrolithiasis

aka renal stones

features: severe spasms of pain (renal colic) and hematuria.

13

Urinary Tract Obstruction

includes renal tumors.

14

4 Stages of Chronic Renal Failure

1. diminished renal reserve: GFR = 50%, serum BUN and creatinine are normal, patients asymptomatic but susceptible to azotemia.

2. renal insufficiency: GFR = 20-50%, azotemia with anemia and HTN, polyuria, nocturia. sudden stress can ⇒ uremia.

3. chronic renal failure: GFR < 20-25%, edema, metabolic acidosis, hyperkalemia. cannot regulate volume and solute composition. overt uremia with neurologic, GI, and cardiovascular complications.

4. end-stage renal disease: GFR < 5%. terminal stage of uremia.

15

Systemic Diseases Associated with Glomerular Disease

diabetes mellitus, SLE, vasculitis, amyloidosis, Goodpasture syndrome, microscopic polyarteritis/polyangiitis, Wegener granulomatosis, Henoch-Schonlein purpura, bacterial endocarditis

16

Glomerulus Anatomy

capillaries

endothelium: thin, fenestrated.

glomerular basement membrane: thick electron-dense central layer (lamina densa), thinner electron-lucent peripheral layers (lamina rara externa and interna).  made of type IV collagen, laminin, proteoglycans (heparan sulfate), fibronectin, entactin, glycoproteins.

visceral epithelium: aka podocytes.  interdigitating processes adherent to lamina rara externa.  foot processes are separated by filtration slits which have a thin diaphragm.

mesangial cells: lies in mesangial matrix.  mesenchymal origin. contractile, phagocytic, and can proliferate, lay down matrix and collagen, and secrete mediators.

17

Normal Glomerular Filtration Barrier Characteristics

  • highly permeable to water and small solutes.  impermeable to proteins like albumin (70kD) or larger.
  • charge selector: more cationic can pass, anionic do not.  determined by proteoglycans of GBM and sialoglycoproteins of epithelial/endothelial cell coats (glycocalyx)
  • slit diaphragm allows for size selection.  important proteins in diaphragm: nephrin, podocin, CD2AP.
  • nephrin connects foot processes by attaching to podocin, CD2AP, and the actin cytoskeleton.

18

Albumin

  • has PI of 4.5.
  • completely excluded from filtrate by size-charge barrier

19

Nephrin

  • part of the slit diaphragm.
  • connects foot processes by attaching to podocin, CD2AP, and the actin cytoskeleton.

20

Podocin

  • part of the foot process of podocytes. 
  • via nephrin, helps link foot processes at slit diaphragm.

21

CD4AP

  • part of the foot process of podocytes.
  • via nephrin, helps link foot processes at slit diaphragm.

22

Hypercellularity

  • in inflammatory diseases of kidney.  
  • characterized by:  cellular proliferation of mesangial or endothelial cells, leukocytic inflitration (neutrophils, monocytes, lymphocytes), and/or formation of crescents

23

Crescents

  • accumulations of cells composed of proliferating parietal epithelial cells and infiltrating leukocytes.  
  • fibrin may elicit the crescentic response.  find it in glomerular tufts and urinary spaces.  
  • others that elicit crescentic formation: tissue factor, IL-1, TNF, IFN-gamma

24

Basement Membrane Thickening

  • on PAS stain: see thickening of capillary walls
  • EM: has two forms:
  • 1. immune complex deposits on endothelial or epithelial side of GBM or within the GBM.  fibrin, amyloid, cryoglobulins, and fibrillary proteins can deposit in GBM.
  • 2. increased synthesis of protein components (see in diabetic glomerulosclerosis).

25

Hyalinosis

  • accumulation of material that is homogenous and eosinophilic by light microscopy.
  • EM: hyalin is extracellular and amorphous.  
  • made of plasma proteins insudated from circulation
  • extensive ⇒ obliteration of capillary lumens of glomerular tuft.
  • consequence of endothelial or capillary wall injury, end result of glomerular damage.  
  • found in focal segmental glomerulosclerosis

26

Sclerosis

  • accumulations of extracelular collagenous matrix, confined to mesangial areas (diabetic glomerulosclerosis) or involving capillary loops.
  • can ⇒ obliteration of capillary lumens ⇒ form fibrous adhesions between sclerotic portions and parietal epithelium and Bowman capsules.

27

Primary Glomerulopathy Categories

  • diffuse = involving all glomeruli
  • global = involving entire glomerulus
  • focal = involves only a portion of the glomeruli
  • segmental = affects part of each glomerulus
  • capillary loop or mesangial = affects predominantly the capillary or mesangial regions.

28

Antibody-associated Injury

  • 1. antibodies reacting in situ within glomerulus, binding to insoluble fixed glomerular antigens or to molecules planted within glomerulus.
  • 2. deposition of circulating antigen-antibody complexes in glomerulus. 

29

Heymann Nephritis

  • on EM: presence of numerous discrete electron-dense deposits along subepithelial aspect of GBM.
  • IF: granular lumpy deposition.
  • results from rxn of antibody with antigen comlex on basal surface of visceral epithelial cells and cross-reacting with brush border antigen. then complement activation and shedding of aggregates to form subepithelial deposits.
  • antigen = megalin = lipoprotein receptor (in rats)
  • anti-GBM antibody induced disease = autoimmune.