Renal Pathology Flashcards
Important Renal Functions
Regulate fluid volume and acid/base balance of plasma
Excrete nitrogenous waste
Synthesize erythropoeitin, 1,25-dihydroxycholecalciferol and renin
Drug metabolism
Healthy Kidney v. Unhealthy Kidney
Healthy Kidney:
- sodium and water removal
- waste removal
- hormone production
Unhealthy kidney
- fluid overload
- elevated waste such as UREA, CREATININE, and POTASSIUM
- changes in hormone levels which control BP, RBCs, and Ca uptake
Definition of End Stage Renal Disease
GFR - less than 5%
Terminal stage of uremia (urine in the blood)
Systemic manifestations of Chronic Kidney Disease and Uremia
Fluid and Electrolytes
(Dehydration- Edema- Hyperkalemia- metabolic acidosis)
Calcium Phosphate and Bone
(Hypocalcemia- hyperphosphatemia- secondary hyperparathyroidism- renal osteodystrophy)
Hematologic
(Anemia- bleeding)
Cardiopulmonary
(Hypertension-HF Cardiomyopaty- pulmonary edema-)
Gastrointestinal
(Nausea and vomiting- gastritis- esopahgities-colitis MYOPATHY- peripheral)
Neuromuscular
(PRURITUS)
Dermatologic
(DERMATITIS)
Comorbidities of Kidney Failure and end stage renal disease
Diabetes
HTN
Glomoerulonephritis
Immunosuppresion
Chronic Kidney Disease (CKD)
Progressive loss or renal function that persists for 3 months or longer
Five stage classification system for CKD based on the glomerular filtration rate (GFR)
CKD Staging
Stage 1) Kidney Damage with normal or increased GFR (90+)
Stage 2) Kidney damage with normal or mild DECREASE in GFR (60-89)
Stage 3) Moderate decrease in GFR (30-59)
Stage 4) Severe decrease in GFR (15-29 GFR)
Stage 5 (end stage) Less than 15% (or dialysis)
Progressive Kidney Disease
Reduced renal function
Effects on multiple organ systems
Potential manifestations of Kidney Disease
ANEMIA ABNORMAL BLEEDING ELECTROLYTE AND FLUID IMBALANCE HYPERTENSION DRUG INTOLERANCE SKELETAL ABNORMALITIES HOST COMPROMISED BY NUTRITIONAL DEFICIENCIES- Leukocyte dysfunction- more susceptibility to infections
Relationship between CKD and bleeding
Decreased production of von Willebrand factor
Platelets dysfunction- abnormal platelet adhesion and aggregation
Defective platelet production
Renal Osteodystrophy
Decreased renal function
Decreased 1,25-dihydroxyvitamin D production
Reduced intestinal absorption of calcium (hypocalcemia)
Secondary hyperparathyroidism
Inhibition of osteoblasts maturation and matrix remineralization
Renal Osteodystrophy Manifestations
Osteomalacia- ummineralized bone
Osteitis fibrosa- bone resorption with lytic lesions and marrow fibrosis
Osteoesclerosis- enhanced bone density
Spontaneous fractures
Slow healing
Bone growth is impaired
Renal Osteodystrophy Signs and Symptoms
Bone pain
Anorexia
Nausea-vomiting
Generalized gastroenteritis and peptic ulcer disease
Peripheral neuropathy- muscular hyperactivity (twitching)
Bleeding- petechiae
Dental findings for Renal Osteodystrophy
Xerostomia Candidiasis Periodontal disease/gingivitis Gingival bleeding Erosion lingual tooth surface Enamel hypoplasia Narrowing of the pulp chambers Pigmentation of oral mucosa Parotid infections Metallic taste Halitosis Ulcerations Lichen/lichenoid lesions Hairy tongue Uremic stomatitis ( in severe end-stage renal disease)
Halitosis
Sign of renal disease due to increased levels of urea in the body
DDX:
- Diabetes
- Respiratory Infections
- Periodontal disease
Clinical Manifestations of Kidney Disease
Azotemia- Increase blood urea and elevated creatinine levels- glomerular filtration rate
Uremia- biochemical abnormalities- manifestations- peripheral neuropathy
Nephritic Syndrome- hematuria- RBC cast moderate proteinuria and HTN
Nephrotic Syndrome- Glomerular disease- HEAVY proteinuria,edema hyperlipidemia and lipiduria
Acute Kidney Injury
Chronic Kidney Disease
Low albumin leads to low oncotic pressure- EDEMA
Leads to increased sodium and water retention
General trend of Kidney Disease etiology
Glomerular- immunologically mediated (Antigen-antibody interactions which deposit circulating antigen-antibody complexes in the glomerulus)
Tubular- interstitial- toxic or infectious agents
Post-infections glomerulonephritis
Caused by immune complexes that contain streptococcal antigens and specific antibodies that are formed in-situ.
Clinical Presentation:
-Abrupt onset of malaise, fever, nausea, oliguria, and
hematuria 1 to 2 weeks after recovery of a sore
throat
- Nephritic syndrome (RBCs in urine)
- Periorbital edema
- Mild to moderate hypertension
-Slight elevation in BUN
Histology:
- Interstitial edema- swelling of endothelial cells
obliteration of the capillary lumens
-Hypercellularity reaction (infiltration of inflammatory
cells, proliferation of endothelial & mesangial cells &
form some crescents…)
- RBC casts in tubules
Immunofluorescence:
Granular deposits of IgG and C3 in the mesangium and along the subepithelial basement membrane
Electron Microscopy:
Discrete, electron-dense deposits on the epithelial side of the membrane; “buzz word” for this is “HUMPS”
Most recover
Goodpasture Disease
antiGBM
Severe glomerular injury characterized by rapid and progressive loss of renal function
Immunological related- antibodies directed at components of the glomerular basement membrane (collagen type lV)
Light Microscopy:
- Hypercellular rxn
- Dominated by Crest formation
- focal or segmental necrosis
Immunofluorescence:*
- Linear deposits of IgG and C3 along the basement
membrane (ribbon-like)
Lung hemorrhage-( pulmonary renal syndrome)
No consistent trigger
Reduced urine output Hemoptysis Edema Recent URI is common Anti-GBM antibody titer- positive
Membranous Nephropathy
Rapid onset of NEPHROTIC syndrome
Chronic immune mediated characterized by diffuse thickening of the glomerular capillary wall
Most cases are Primary (75%):
- NSAIDs- gold- captopril- penicillamine- SLE
-Malignancies ( lung-colon-melanoma) lymphoma
-Infections (hepatitis) syphilis
- Other autoimmune disorders like Sarcoidosis-
Sjogren- RA
Immunofluorescence:
Accumulation of diffuse, granular deposits of IgG and C3 along the subepithelial side of the basement membrane, in situ
EM:
- Basement membrane material is laid down between the deposits formed between the basement membrane and the overlying epithelial cells with effacement of podocyte processes; buzzword is “SPIKES”
Minimal Change Disease
Benign NEPHROTIC disorder seen in children 2-6 years of age
90% idiopathic- thought to be likely involved wih immune system dysregulation
Glomerular injury-increase glomerular permeability
Massive proteinuria with perserved renal function; mostly Albumin is lost
GFR normal
Sometimes after a respiratory infection or immunization
GOOD RESPOND TO CORTICOSTEROIDS***
Renal biopsy- Electron microscopy- podocyte effacement. Normal by light microscopy
Frequent lipid and protein in the proximal tubules called “LIPOID NEPHROSIS”
Immunofluorescence:
No Ig or complement deposition
Common symptom of Minimal Change Disease
Periorbital Edema
Focal Segmental Glomerulosclerosis
Most common Nephrotic syndrome in adults in the US (children can be affected)
Acute or subacute onset
Higher incidence of hematuria, reduced GFR, hypertension, azotemia.
Proteinuria is more non-selective
POOR RESPONSE TO CORTICOSTEROIDS
50% progress to ESRD in 10 years
Similar presentation to minimal change
More common in black people 4-7 fold increase. More men than females
Principal etiology of ESRD- sclerosis progresses- GLOBAL sclerosis**
Focal Segmental Glomerulosclerosis etiology
Incidence of primary and secondary forms has been increasing steadily
May be secondarily assoc with HIV, heroin nephropathy, sickle cell dz, and morbid obesity
As a secondary event
- Scarring from a previous necrotizing event
Adaptive response to loss of renal tissue
- Congenital abnormalities, reflux nephropathy, hypertension
Uncommon inherited form of nephrotic syndrome linked to mutations in genes that encode the protein products nephrin and podocin.
What is the hallmark of FSGN on histology?
epithelial damage
Light micro: focal and segmented lesions; mesangial collapse and sclerosis
Electron micro: Degeneration and focal
disruption of epithelial cells with diffuse effacement of foot processes, (podocytes)
Immunofluorescence:
IgM and C3 in the sclerotic areas and the mesangium
Difference between Minimal Change Disease and FSGN
Spontaneous remission is rare
Children have a better prognosis with Minimal Change Disease
Poor response to corticosteroids therapy in FSGN
Whereas minimal change disease (MCD) shows normal histology, FSGS is associated with sclerosis under the microscope with proteinuria.
Progression to chronic kidney dz, with 50% developing ESRD within ten years
IgA Nephropathy (Berger Disease)
Common worldwide (most common glomerulonephritis)
Mesangial IgA immune deposits
Glomerulonephritis of varying severity
Idiopathic or after an upper respiratory tract infections or gastroenteritis; gross hematuria
Hematuria lasts a few days, subsides, and returns every few months
Maintain normal kidney function for decades
15-40% will develop chronic renal failure over a period of 20 years
Occurs with increased frequency in individuals with gluten enteropathy and liver disease
5-10% develop acute nephritic syndrome with some developing rapidly progressive glomerulonephritis
Alport Syndrome
Defective type IV collagen- glomerular basement membrane
X linked autosomal dominant/autosomal recessive forms exist
Nerve deafness, lens dislocation, posterior cataracts and corneal dystrophy
Manifested by hematuria and progression to chronic renal failure
Males
Variability age of onset
EM: Irregular thickening and thinning of the GBM with splitting and lamination of the lamina densa
Buzzword: “Basketweave appearance”
Diabetic nephropathy
Leading cause of CKD
ESRD occurs in up to 40% of diabetics
Histopath changes are similar for type I and type II diabetics
Three lesions are encountered:
Glomerular
Renal vascular (arteriolosclerosis)
Pyelonephritis
Diabetic microangiopathy- glomerular lesions and thickening of basement membranes
Pyelonephritis (kidney infection spreading from UTI)
Causes of Secondary Glomerulonephropathies
SLE- 50 % renal involvement
(predominant effects females)
Diabetes- arteriolosclerosis- microangiopathy- pyelonephritis
Sickle cell disease
Lupus Nephritis
Renal disease in > 50% of patients
Clinical Presentation: Persistent proteinuria
Nephritic synd; Nephrotic synd; Rapidly Progressing Glomerular Nephritis; Membranous; Acute and chronic renal failure
Pathogenesis: Immune complex deposition;
Anti-dsDNA antibodies deposited within the mesangium and non-uniformly along the basement membrane
In situ and immune complex deposition
Wide variability in injury patterns
Six different classes of systemic lupus classified pathologically
Lesions seen in Diabetic Nephropathy (Kimmelstiel- Wilson Disease)
Glomerular lesions:
Capillary BM thickening
Diffuse mesangial sclerosis
Nodular glomerulosclerosis
Tubular lesions:
BM thickening
Microangiopathy:
- Hyaline sclerosis of the afferent and efferent arterioles
