Renal: Pathology Flashcards
1
Q
- Kidneys connected at the Lower Pole
- Most common congenital Renal anomaly
- Abnormally located in the Lower abdomen
- Gets caught on the Inferior Mesenteric Artery root during Ascent from the Pelvis → Abdomen
A
Horseshoe Kidney
2
Q
- Absent Kidney formation → Unilateral or Bilateral
- Unilateral agenesis – hypertrophy of the existing Kidney and Hyperfiltration leads to increase risk of Renal failure later in life
- Bilateral agenesis – Oligohydramnios w/ Lung Hypoplasia, Flat Face, and Low ears and developmental defects of extremities (Potter Sequence) = incompatible w/ Life
A
Renal Agenesis
3
Q
- A condition in pregnancy characterized by a deficiency of amniotic fluid. It is the opposite of polyhydramnios
- The breathing of the amniotic fluid helps stretches the babies lungs and helps to promote lung development – w/out the lungs fail to develop correctly
A
Oligohydramnios
4
Q
- Noninherited, Congenital malformation of the Renal Parenchyma characterized by Cysts, and Abnormal tissue (e.g. cartilage)
- Usually unilateral
- Bilateral – MUST be distinguished from Inherited Polycystic Kidney disease
A
Dysplastic Kidney
5
Q
- Inherited defect – Bilateral enlarged Kidneys
- Cysts in the Renal Cortex and Medulla
-
Autosomal Recessive - PKHD1 (6q21-p23)– form presents in infants as worsening Renal failure and Hypertension
- Newborns present w/ Potter Sequence
- Congenital Hepatic Fibrosis (Portal Hypertension)
- Hepatic cysts – in the Liver and Kidney
- Newborns present w/ Potter Sequence
-
Autosomal Dominant – Young Adults as Hypertension due to increased Renin, Hematuria, and Worsening Renal Failure
- Mutations APKD1 (16p13.3) or APKD2 (4q21) genes – cysts develop over time
- A/w Berry aneurysm, Hepatic cysts, Mitral valve prolapse
A
Polycystic Kidney Disease (PKD)
6
Q
- Inherited disease causing Tubulointerstitial fibrosis and Progressive Renal Insufficiency w/ inability to concentrate urine
- Autosomal dominant defect leading to Cysts in the Medullary collecting ducts
- Parenchymal Fibrosis results in Shrunken Kidneys and woresening Renal Failure
- Poor prognosis
A
Medullary Cystic Kidney Disease
7
Q
- Acute, Severe decrease in Renal Function (develops w/in Days) as measured by GFR (Normal 115 - 125 mL/min
- Hallmark is Azotemia (↑ BUN and ↑ Creatinine [Cr], often w/ Oliguria (Urine < 500 mL/day) or Anuria (Urine < 100mL/day)), Polyuria (> 3 L/day)
- Increase in nitrogenous waste production
- Divided into PreRenal, PostRenal, and IntraRenal based on etiology
A
Acute Renal Failure (ARF)
8
Q
- Decreased Blood flow to Kidneys (e.g. cardiac failure) → common cause ARF
- ↓ RBF → ↓ GFR – Azotemia and Oliguria - ↓ Urine production - Na+ / H2O and Urine retained
- Reasbsorption of Fluid and BUN ensues (serum BUN:Cr ratio > 15); Tubular function remains intact (Fractional excretion of Na [FENa] < 1% and Urine osmolality [osm] > 500 mOsm/kg – The Kidneys still have the ability to concentrate the Urine **Urine Na < 10 **(mEq/L) **
A
Prerenal Azotemia
9
Q
- Due to Obstruction of Urinary Tract downstream from the Kidney (e.g. Ureters)
- ↓ GFR – Azotemia, and Oliguria
-
Early stage obstruction, increased Tubular pressure “forces” BUN into the blood - Urine Na+ < 20 mEq/L
- (serum BUN:Cr ratio > 20); Tubular function remains intact
- (FENa < 1% and Urine [osm] > 500 mOsm/kg – tubules still function
-
Long stage obstruction, Tubular damage ensues, resulting in decreased reabsorption of BUN
- (serum BUN:Cr ratio > 15)
- Decreased reabsorptoin of sodium (FENa > 4%) and Urine [osm] < 350 mOsm/kg, Urine Na > 40 mEq/L
A
Postrenal Azotemia
10
Q
- Injury and Necrosis of Tubular Epithelial cells
- Most common cause of Acute Renal Failure (ARF) (intrarenal azotemia) may have Oliguria and Azotemia
- A/w Rhabdomyolysis and Crush injury
- Necrosis cells plug Tubules; Obstruction decreases GFR
- Muddy-brown, Granular, Casts are seen in the Urine
- Dysfunctional Tubular Epithelium results in Decreased Reabsorption of BUN (serum BUN:Cr ratio < 15)
- Decreased reabsorption of sodium (FENA > 2%)
- Inability to concentrate Urine (Urine [osm] < 500 mOsm/kg)
A
Acute Tubular Necrosis
11
Q
- Decreased blood supply results in Necrosis of Tubules (decreased ATP leads to ischemia)
- A/w rupture of the Basement membrane (Tubulorrhexis)
- 1st: Often Preceded by Prerenal Azotemia
- Proximal Tubule and Medullary segment of the Thick Ascending Limb are particularly Susceptible to Ischemic Damage
A
Ischemic Acute Tubular Necrosis
12
Q
- Toxic agents result in Necrosis of Tubules
- Proximal tubule is particularly susceptible
- 2nd: Causes include Aminoglycosides (most common), Heavy metals, Myoglobinuria (crush inj.), Ethylene glycol (a/w oxalate crystals in urine), Radiocontrast dye, Urate, Tumor lysis syndrome
- Hydration and Allopurinol are used prior to initiation of Chemotherapy to Decrease risk of Urate-induced ATN
- Dx: Oliguria (2-3 weeks before recovery, regen.) w/ ‘Muddy’ Brown Granular casts
- Elevated BUN and Creatinine
- Hyperkalemia w/ Metabolic acidosis – decreases excreating of organic acids – Anion gap
- Tx: Reversible but requires Supportive Dialysis since Electrolyte imbalance – Fatal (Oliguric phase)
A
Nephrotoxic Acute Tubular Necrosis
13
Q
- Drug-induced Hypersensitivity involving the Interstitium and Tubules - acting as Haptens
- Results in Acute Renal Failure (intrarenal azotemia)
- Caused by NSAIDS, Penicillin, and Diuretics
- Presents w/ Oliguria, Fever, and Rash days to weeks after starting a drug; Eosinophils and Azotemia may be seen in Urine
- WBC casts
- Resolves w/ cessation of drug
- May progress to Renal papillary necrosis
A
Acute Interstitial Nephritis
14
Q
- Necrosis of Renal papillae ‘sloughing’
- Presents w/ Gross Hematuria and Flank Pain
- Polyuria, Rust-colored urine, ARF, Sediment, Casts
- CXR - Ring of calcification (neprocalcinosis)
- Causes include:
- Chronic Analgesic abuse (long term Phenacetin or Aspirin use) (Acetaminophen is a derivative)
- Diabetes mellitus
- Sickle cell traits or Disease
- Severe Acute Pyelonephritis
A
Renal Papillary Necrosis
15
Q
-
Glomerular disorders characterized by Proteinuria (> 3.5 g/day) resulting in:
- Hypoalbuminemia – pitting edema
- Hypogammaglobulinemia – increased risk of infection – protein in blood
- Hypercoagulable state – due to loss of Antithrombin III – loss of anti-coagulant protein – breaking up of thrombi and prevention of thrombi anti-coagulet
- Hyperlipidemia and Hypercholesterolemia – may result in Fatty Casts in urine – thin blood – Liver adds Fat to Thicken the blood
A
Basics of Nephrotic Syndrome
16
Q
- Most common cause of Nephrotic syndrome in Children (idopathic) (80%)
- Usually Idiopathic; may be a/w Hodkin lymphoma (cytokine-mediated damage)
- Normal glomeruli on H&E stain; Lipid may be seen in Proximal tubule cells - “Lipoid nephrosis” - ‘Foamy’
- Effacement of Foot processes on electron microscopy
- No immune complex deposits; negative immunofluorescence – not deposit mediated
- Selective Proteinuria (Loss of Albumin, but not immunoglobulin)
-
Excellent response to Corticosteroids (knock out cytokine production) (damage is mediated by cytokines from T cells)
- Hodgekins Lymphoma – overproduction of cytokines by Reed-Sternberg cells – Fever, Chills, Night sweats
A
Minimal Change Disease (MCD)
17
Q
- Most common cause of Nephrotic Syndrome in Hispanics and African Americans
- Usually Idiopathic; may be a/w HIV, Heroin use, and Sickle cell disease, Massive obesity, INF treatment
- **Focal accumulation of Hyaline material (<50%) **(some glomeruli) and Segmental Sclerosis (involving only part of the glomerulus) – sclerosis on H&E stain
- Effacement of Foot processes on EM
- No immune complex deposists; Negative IF
- Poor response to steroids -> Cyclophosphamide and Cyclosporine -> Progresses to Chronic Renal Failure
A
Focal Segmental Glomerulosclerosis (FSGS)
18
Q
- Most common cause of Nephrotic syndrome in Caucasian Adults
- Usually idiopathic; may be a/w Hepatitis B and C, Solid tumors, SLE, Rheumatoid arthritis, Syphilis, Schistosomiasis, Malaria, Leprosy, **Phospholipase A2 receptor, **Drugs (NSAIDs and Penicillamine)
- GBM Thickening on H&E w/ ‘Spike and dome’
- Due to Immune Complex Deposition (granular IF; subepithelial deposits), and Nephrotic SLE
- Poor response to Steroids progresses to Chronic Renal Failure
A
Diffuse Membranous Glomerulopathy
19
Q
- Thick Glomerular basement membrane on H&E, often w/ ‘TRAM-Track’ appearance - Hypercellular glomeruli
- Immune Complex Deposition (granular IF)
- Dividied into (2) Types based on Location of Deposits
- Type I – Subendothelial (**HBV, **HCV, Cryoglobulinemia) (Type III Hypersensitivity)
- Type II – “dense deposit disease” – Intramembranous; a/w C3 Nephritic Factor (auto-Ab that Stabalizes C3 Convertase, leading to Overactivation of Complement, inflammation, and Low Levels of circulating C3), No IgG present
- Poor response to Steroids; progresses to Chronic Renal Failure
A
Membranoproliferative Glomerulonephritis
20
Q
- High Serum glucose leads to Nonenzymatic glycosylation of the Vascular basement membrane resulting in Hyaline arteriolosclerosis (basement membrane becomes Leaky – leaking protein – Hyaline prolif.) -> mesangial expansion
- Glomerular Efferent >> Glomerular Afferent in the Arteriole – leading to High Glomerular Filtration process
- Hyperfiltration injury leads to Microalbuminuria
- Eventually progresses to Nephrotic Syndrome
- Characterized by Sclerosis of the Mesangium w/ formation of Kimmelstiel-Wilson nodules
- ACE inhibitors slow progression of Hyperfiltration-induced damage
A
Diabetic Nephropathy
21
Q
- Kidney is the most commonly involved organ in Systemic Amyloidosis
- Amyloid deposists in the Mesangium, resulting in Nephrotic Syndrome
- Characterized by Apple-green Birefringence under Polarized light after straining w/ Congo red
A
Systemic Amyloidosis
22
Q
- Glomerular Inflammation and Bleeding -> Hematuria
- Mild Proteinuria (< 3.5 g/day)
- Oliguria (< 400 mL/day) and Azotemia (↑ BUN and Creatinine) – decrease in urine and increase in nitrogenous waste products w/in the blood
- RAAS w/ Periorbital / Pitting Edema and Hypertension
- RBC casts and Dysmorphic RBCs in urine
- Biopsy reveals Hypercellular, Inflamed glomeruli
- Immune-complex deposition activates complement; C5a attracts Neutrophils – which Mediate damage – Hypercellularity
- **C3 levels, anti-GBM titer, **and ANCA titer
A
Nephritic Syndrome
23
Q
- Nephritic syndrome w/ Group A β-hemolytic Streptococcal Infection of the skin (impetigo) or pharynx - ‘**Starry-sky’ **appearance - Type III Hyper.
- W/ Nephritogenic strains – Carry **M protein Virulence Factor - Serum chemistry -> Antitreptolysin-O **and anti-DNAase B are elevated, ANCA and anti-GBM neg.
- After Infection w/ Nonstreptococcal organisms as well
- Presents 2 -3 weeks after infection as Hematuria (cola-colored urine), Oliguria, Hypertension, and Periorbital edema -> “Smokey-brown” or “Cola-colored” urine
- Usually seen in Children but may occur in Adults
- Hypercellular, inflamed Glomeruli on H&E
- Mediated by immune complex deposition (Granular IF); Subepithelial ‘humps or lumpy-bumpy’ on EM
- Tx: Children rearely (1%) profress to Renal Failure
- Some Adults develop Rapidly Progressive Glomerulnephritis (RPGN) (wks – mths)
A
Poststreptococcal Glomerulonephritis (PSGN)
Acute Proliferative Glomerulonephritis
24
Q
- Malignant form of Nephritic syndrome that progresses to Renal Failure in Weeks to Months
- Characterized by Crescents in Bowman space (of Glomeruli) on H&E stain
- Crescents are comprised of Fibrin and Macrophages
- Clinical picture and IF help resolve etiology
- (3) Distinct Types:
- Goodpasture syndrome - Type II, ANCA-negative
- Poststrep GN, SLE, IgA neph. Henoch-Schonlein purpura - ANCA-negative - Type III
- Wegener granulo. or ideopathic - PR3-ANCA / c-ANCA - positive
A
Rapidly Progressive Glomerulonephritis
25
Q
- IgA immune complex deposition in Mesangium of Glomeruli
- Most common nephropathy worldwide
- Presents during Childhood as Episodic Gross or Microscopic Hematuria w/ RBC casts
- Usually following Mucosal Infection – IgA production in increased during Infection, a/w Hnoch-Schonlein purp.
- IgA immune complex deposition in the Mesangium is seen on IF – glomerular bleeding
- Every episodic infection you get bleeding from the Kidney a/w Celiac disease
- Slow progress to Renal failure
A
IgA Nephropathy (Berger Disease)
