What causes Sickle Cell Pain Crisis?
• what are some key lab values you would expect to see in this disease?
Sickle Cell Crisis:
• Vasoocclusive Phenomenon
Key Labs (outside of peripheral smear):
• Elevated Reticulocytes
• Elevated Lactate Dehydrogenase and Bilirubin
Smear would show:
• Howell Jolly Bodies from Splenic Infarcts and Sickled cells
What percentage of Sickle Cell Patients will progress to end stage renal disease?
4-12% - these patients are hard to take care of because you have anemia on top of renal dysfunction
What type of Renal Pathology would you expect to see in someone with Sickle Cell Nephropathy at different points in disease progression:
• End Stage
• Focal areas of cortical injury, Hemorrhage and Necrosis with Glomerular Hypertrophy
• TUBULAR atrophy and Papillary Infarcts
• Focal Segmental Glomerulosclerosis
***Really you're just getting infarcts in the cortex (peritubular capillaries) that also progress through the vasa recta causing ischemia and decreased absorption, eventually tubular dysfunction leads to a decreased GFR.
T or F: what is shown here is Chronic Injury due to Sickle Cell.
• KEY FEATURES?
FALSE, this is acute injury, all you see is CONGESTION of peritubular capillaries and ACUTE TUBULAR NECROSIS (notice nuclear fallout on both of these images)
note front and back are both Acute Sickle Cell Nephropathies
What immune complexes will stain positive in Sickle Cell Nephropathy?
• Key features on silver staining?
• NONE, sickle cell nephropathy is not associated with immune complex deposition
• Silver Staining Key Features - Duplication of the Basement membrane
How do you differentiate this silver staining from Membranoproliferative Glomerulonephritis type I based on the image below?
• Serological studies?
Shown here is Sickle Cell disease you can see sickeled cells inside the glomerular capillaries
• Immunoglobulins/ Low C3 levels will be present in MPGN type I, this is not the case in sickle cell
Is the image shown below more indicative of acute or chronic sickle cell disease?
CHRONIC - you can see severe sclerosis of the glomeruli here
What are the key features seen in this EM from a sickle cell patient?
Podocyte Food Process Effacement
• Impacted cell also suggest an abnormal amount of clotting within the glomerulus
What cancer of the Kidney is EXCLUSIVELY associated with sickle cell patients?
MEDULLARY CARCINOMA OF THE KIDNEY
• VERY POOR these pts. typically present with Metastatic cancer and die in 4-6 months
• Cancer is typically localized to the RIGHT kidney
What 3 chronic kidney diseases actually cause ENLARGMENT of the kidney?
• why is this unusual?
ENLARGMENT of the kidney:
• Renal Amyloidosis
• Diabetic Nephropathy
• HIV associated Nephropathy
What Disease is shown here?
• how does kidney disease progress in a patient who shows thiss?
RENAL AMYLOIDOSIS - any type
Progression: Tubular and Interstitial Deposits may lead to TUBULAR atrophy and INTERSTITIAL fibrosis
What type of Amyloidosis should you suspect in someone who has Rheumatoid Arthritis and nephrotic syndrome?
AA amyloid, it associated with diseases of chronic inflammation
What type of amyloidosis should you suspect in a person who has polyneuropathy and family history of amyloidosis?
ATTR - transthyretin type of amyloidosis runs in families
What type of amyloid should you suspect in a patient with 'shoulder pads' and glossomegaly?
AL amyloid - deposition of restricted immuno light chains
What disease associations should you make with AL amyloid?
• Multiple Myeloma
• Waldenstrom's Macroglobulinemia
What disease associations should you make with AA amyloid?
Any disease that causes chronic Inflammation or Infection
Who gets ß2-microglobulin amyloidosis?
• typical sight of deposition?
• People with CHRONIC KIDNEY DISEASE/ PEOPLE on DIALYSIS
• Tends to deposit in the Joints
After seeing apple green birefringence on Congo Red Staining of Biopsy, how can you confirm the type of amyloid you're dealing with?
• Immunohistochemistry is typically enough
• Need to show MONOCLONAL proliferation in the Bone or Kappa or Lamba restricted light chains in the tissue biopsy
• Need to do a DNA test
AL Amyloidosis Nephropathy:
• who are you most likely to see it in?
• Kidney size? HTN? Other problems?
• Mean age is 64 y/o - these pts. probably have cancer/pre-cancer
• Kidney is enlarged in this condition (b/c its an amyloidosis)
• NO hypertension associated with this disease
**Restrictive Cardiomyopathy and GI immotility may also be issues for these patients
What is the prognosis after getting diagnosed with PRIMARY AL amyloid?
• What are your treatment options?
Px: BAD, most pts. only live 10 months after diagnosis
Patients under 50:
• Melphalan and get a Stem Cell transplant
Patients over 50:
• Melphalan + Dexamethasone
Patients with what type of AL amyloidosis have the greatest chance of developing Multiple Myeloma?
• I Chain AL amyloidosis is most associated with this
What is shown here?
Bence Jones proteins can precipitate in the urine or in the tubules and the tubular epithelial cells can coalesce into a syncytium around them:
Shown Below is a Bone Marrow Biopsy of a Patient with amyloidosis
What is the main target organ for AA amyloidosis?
• What is the newest treatment option?
• what typically causes death in these patients?
Main Target Organ:
1st = Kidney
2nd = GI
(compare to AL that also targets the hrt)
Eprodisate - Prevents interaction between GAGs needed to form amyloid sheets (does not improve survival)
• Typically related to infection from dialysis
What is this patients' biggest risk factor for experiencing this injury?
This is a ß2 microglobulin defect that deposits in BONE leading to destruction
DIALYSIS patients are the people most often seen with this
Below you can see an H and E of this disease
What is Light Chain Deposition Disease?
•what is it associated with?
• Amyloid Staining? explain.
Light Chain Deposition Disease:
• Associated with: MULTIPLE MYELOMA
This DOES NOT complex to form chains that are characteristic of amyloid this means it also WILL NOT STAIN WITH THE CONGO RED DYE
How might someone with light chain syndrome present?
•Proteinuria and renal failure
•May have non-nephrotic range proteinuria with a tubulointerstitial syndrome
•May present with rapidly declining renal function
•May have hepatomegaly
•Cardiomegaly, CHF, conduction disturbances
•Peripheral neuropathy, GI disturbances, pulmonary nodules, arthropathy, sicca syndrome
What are the Key Features of the Image seen here?
• what should be in your differential for this image?
• NODULAR Glomerulosclerosis
• Deposition along the outside of the Tubular Membrane
• Expansion of the Mesangial Matrix
• Light Chain Deposition Disease
• Diabetic Nephropathy
Shown here is a Kappa light chain stain.
• Key features?
1. Kappa Restriction suggests pathology
2. Can see NODULAR Glomerulosclerotic appearance
Dx: Light Chain Disease
What should raise suspicion of a patient having Light Chain Disease?
•Increased index of suspicion with nephrotic syndrome or rapidly progressive tubulointerstitial nephritis, cardiac diastolic dysfunction, and presence of monoclonal immunoglobulin in the urine or serum
• Type of Neuropathy? What distinguishes it from others of this type?
• Who does this occur in most often?
COLLAPSING Focal Segmental Glomerulosclerosis mostly occurs in AFRICAN AMERICANS
**MYCROCYSTIC DILATED TUBULES with PODOCYTE PROLIFERATION and Interstitial inflammation distinguish this from other FSGS types
Besides HIVAN, what else can cause Microcystic Tubular Dilation and podocyte proliferation in FSGS?
What viral Genes are believed to be key in causing HIVAN?
• genes that make African Americans Susceptible?
• Nef and Vpr - cause DE-differentiation of podocytes
African American Susceptibility:
• APOL1 related
What should you be thinking when you see the following clinical features?
•Advanced HIV disease
•Rapid decline in kidney function
HIVAN - behind sickle cell, this is the most common cause of End Stage Renal Disease in young African Americans
What cause glomerular collapse in HIVAN?
FSGS leads to collapse because of PODOCYTE (visceral epithelial) overgrowth
What is shown here?
• KEYYYY terms?
Collapsing FSGS from HIVAN
• This shows the MICROCYTIC**** tubular interstitial appearance (lots of little holes to the left)
• On the far right in the middle you can see collapsed glomeruli
What triad is associated with Cryoglobulinemia?
• markers found in serum?
• Disease association?
• Persistence of the disease?
• Palpable Purpura
Rh factor and Cryoglobulins are key
• 90% of cases are associated with Hepatitis C
• Described as Waxing and Waning
• Immune Complex Disease?
• Kidney Pathology?
• Presence of Proteinuria or Hematuria?
•Renal disease usually due to immune complex disease
•Was the cause of biopsy proven glomerulonephritis
•Membranoproliferative glomerulonephritis is the typical renal biopsy finding
•Isolated proteinuria or hematuria occurs much more frequently than nephrotic or nephritic syndromes or acute renal failure.
•Most patients declare a chronic or rapidly progressive disease course within three to five years of diagnosis
Where does Cryglobulinemia tend to affect the kidney?
Intralobular Arteries and Afferent Arterioles
See Below: deeply acidophilic material in the vessel probably is a mixture of thrombus, fibrinoid necrosis, and aggregated cryoglobulins. The vessel wall and adjacent tissue are infiltrated by leukocytes with leukocytoclasia.
In acute cases, the deposits produce the appearance of thrombi or wire loops comparable to what is seen in lupus glomerulonephritis.
What do you expect to see on immunofluorescence of Cryoglobulinemia?
• what immuno stain should you probably use?
GLOBULAR APPEARANCE of Cryogloblulins most often is C3
What key Feature on this EM lets you know that its Cryoglobulinemia?
Fibrillary Appearance in the SUBEPITHELIUM