Renal Vascular Diseases Flashcards
What are the common findings in renal vascular dz?
Microangiopathic hemolytic anemia
Thrombotic microangiopathy
Coagulation
Damage to endothelium
Platelet count falls
Signs of intravascular hemolysis: i.e. LDH high
Hemolytic Uremic Syndrome: what causes it? pathogenesis?
Secondary to shiga toxin after E. coli infection
Toxin: A subunit binds ribosome, inhibits protein synthesis
5B subunits bind glycolipid receptors gb3 on surface of colonic epithelium, endothelium, and WBCs
Also causes release of cytokines and vWF
For the kidneys– damage to the endothelium causes microangiopathic hemolytic anemia
Hemolytic Uremic syndrome: histological findings
Fibrin/RBC thrombi in glomerulus
Cortical necrosis
Necrotic tubules
No immune deposits, but you see fibrin deposits on immuno stain
Widening of subendothelial space in less severe cases
Hemolytic uremic syndrome: typical lab values
Low platelets
High creatinine
High LDH
For those with E. coli infection, which factors put you at a higher risk of developing HUS?
Antibiotics
Bloody diarrhea
Fever, vomiting
Leukocytosis
<5 yo
females
What is the treatment and course of HUS?
Supportive treatment (antibiotics are controversial)
Outcome of childhood HUS:
50% dialysis
75% transfusions
25% neuro sx- CVA, sz, coma
3-5% die in acute phase
long term renal dysfunction common
3-18% ESRD
10-40% low GFR, proteinurea, chronic renal failure, high bp
Duration of anuria predicts dysfunction
Atypical hemolytic uremic syndrome i.e. diarrhea negative hemolytic uremic syndrome: cause/pathogenesis?
It’s a disease of the complement system: continuous activation of the alternate complement system due to genetic defects and/or antibodies that alter the action of these complement regulatory proteins
Factors involved: Factor H, Factor I, or MCP
Atypical hemolytic uremic syndrome: treatment
- *Eculizumab**: humanized antibody that binds C5 with high affinity & blocks its activity
- leads to normal platelet count & normal LDH
- elimination of plasma exchange/infusion
- no new dialysis
- proximal functions of complement remain intact
Liver transplant along with kidney transplant
**Replaces the missing complement inhibitor so that you don’t get a recurrence in the transplant patient
TTP: cause/pathogenesis?
Reduced levels of ADAMTS13 (enzyme that cleaves vWF) –> huge vWF multimers –>
Can be familial (mutations) or acquired (autoantibody)
Can be single episode or relapsing
Female 2: Male 3, Peak in 3rd decade
CNS & other extrarenal signs often predominate
Acute renal failure (more common in this dz than in the others), microangiopathic hemolytic anemia, thrombocytopenia
** Systemic manifestations are more common in TTP than in HUS **
TTP: lab values?
Smear shows microangiopathic hemolytic anemia
- schistocytes
Low platelets
Low hematocrit
Normal PT and normal PTT
TTP: treatment?
Plasma exchange = Plasmapheresis
Removes the bad stuff i.e. if you have an antibody against ADAMTS13
Adds back good stuff i.e. VWF, platelets
TTP: histological findings?
Glomeruli and arteriole with thrombus in the middle
Thrombi made of platelets and RBC’s
Entrapped RBCs in arteriole wall = multiple layers of myofibroblasts
Feature of both actue thrombosis and chronic organizing
Antiphospholipid Antibody Syndrome aka anticardiolipin syndrome - cause?
Antibody (mainly IgG, could also be IgM, IgA) against negatively charged phospholipids
What lab findings for antiphosphilipid antibody syndrome?
Positive for antiphospholipid antibodies
- *Prolonged PTT, normal PT**
- this is bc the antibody interferes with the PTT assay in vitro, it has nothing to do with what happens in vivo
Antinuclear antibody (ANA) +
Anti-DNA
Low complements
False positive VDRL
Hypertension, active urinary sediment, elevated crat, proteinurea, nephrotic syndrome: seen in pt’s at biopsy
Antiphospholipid andibody syndrome: pathological/histological findings?
Acute and chronic thrombotic angiopathy
Glomeruli show ischemic changes: global wrinkling of glomerular basement membranes, tuft retraction, cystic dilation of Bowman’s space
Glomeruli have intracapillary fibrin & RBC thrombi
Arterioles also have fibrin & RBC thrombi
Mesangiolysis = loose, widened mesangium
Subactue/chronic changes: arteries show widespread luminal narrowing with mucoid intimal fibroplasia and entrapped RBCs
Which antibdies can you find in antiphospholipid antibody syndrome?
IgG, IgM, IgA against negatively charged phospholipids that includes:
Lupus anticoagulant: Abs that proling lipid-depending coagulatoin tests, interfere with phospholipid of the prothrombin activator complex
Anticardiolipid antibodies: bind cardiolipin (phospholipid antigen used in tests for syphilis) –> false positive VDRL
** all have a procoagulant effect in vivo
Which underlying conditions are associated with antiphospholipid antibodies?
Systemic lupus erythematosus
- full blown lupus
Lupus-like syndrome
- mostly young women
Primary anti-phospholipid antibody syndrome
- mostly older men
What are the clinical manifestations of anti-PL ab syndrome?
Recurrent arterial and venous thromboses
Placental thromboses and recurrent abortions
Livedo reticularis
CNS complications
Pulmonary hypertension
Chronic kidney failure
Hypertension
Rarely: catastrophic APL syndrome = actue kidney failure+
What is livedo reticularis?
Commonly seen in antiphospholipid antibody syndrome
What external manifestations can you seein antiphospholipid antibody syndrome?
CNS dz
DVT
MI
Pulm embolism
Livedo reticularis
Adrenal dz
Aortic thrombosis
Bowl infarction
Miscarriage
What is the treatment for antiphospholipid antibody syndrome? What’s the course of the dz?
Treat with anticoagulation therapy
Few have true systemic lupus erythematosus (SLE)
Half have improved renal function
Most have remission of nephrotic syndrome
27% worsening function
15% ESRD
Renal atheroembolic dz + hypertensive arterionephrosclerosis- what is it?
- *Renal atheroembolic dz**: cholesterol emboli in small vessels of kidney: frequent complication of pt’s who have severe atherosclerosis & get an invasive procudure i.e. vascular procedures like putting a stent in
- has the same effect as a thrombus: blocks flow into kidneys
Hypertensive arterionephrosclerosis: hypertension –> changes in the kidney: shrunken kidney, finely granular surface grossly, thin renal cortex, normal medulla, thickenend walls of arterioles, narrowed vessels –> chronic ischemia –> wrinkling of mesangium & fibrosis & necrosis
What are the clinical features of renal atheroembolic dz?
Acute renal failure
Rash, eosinophilia
Other organs can be involved: skin, GI tract
May develop renal infarction in severe cases
Chronic ischemic nephropathy more commonly
