Vascular diseases and TIN Flashcards
What happens in minimal change disease?
Minimal change disease total effacement of foot processes after they fuse due to electrical charge displacement.
is it better to diagnose someone with nephritic synd?
Nephritic syndrome is almost always due to glomerulonephritis. Acute renal failure is a useless diagnosis
What are the types of crescentic GN?
Type 1 2 and 3 crescentic glomerulonephritis
as
antiglGBM disease presents with people having anti alpha 3 chain type 4 antibodies GBM
pulmonary-renal syndrome
immunofluorescence IgG antibodies
electron microscopy does not show the complexes due to low resolution of the interaction
ac
pauci immune glomerulonephritis
anti-neutrophil cytoplasmic antibody
autoantibodies against enzymes in the cytoplasm of neutrophils
small vessel vasculitis
Wegener granulomatosis, Churg-strauss syndrome
crescents in histology
no immune complexes on immunofluorescence nor electron microscopy
cc
hypertensive nephrosclerosis is damage done due to High BP. 2 types; benign due to chronic hypertension malignant.
renal disease can cause HBP and vice versa (viscious cycle)
malignant hypertension can be completely de novo. bp 180/110. BP should be dropped urgently but in a controlled way. severe damage to arteries and ischaemic damage. fibrinoid necrosis of arterioles. hyperplastic arteriolopathy. (onion skinning)
benign HT nephrosclerosis is caused by thickening of the walls of the small arteries and arterioles of the kidneys causing smaller lumen and in turn ischaemic damage to glomerulus and tubular atrophy as well as interstitial fibrosis. Can result in surface granularity on the kidneys. thickening of intima and media arterioles become damaged and leaky and plasma protein trapped in wall of arteriole this is known as hyalinosis
atrophic
a
renal artery stenosis is an uncommon cause of secondary hypertension. narrowing in one of the renal arteries (in elderly caused by atherosclerosis) kidney recognizes low oxygen and responds with more renin creating ANG2 which will constrict all the arteries in the circulation rasining BP altogether.
ACE inhibitor use this mechanism.
Fibromuscular dysplasia causes intermittent (back and forth) thickening of renal artery until kidney.
a
acute tubular necrosis most common cause of renal failure. Toxic causes (endogenous which are native to the body and exogenous which are from elsewhere) and ischaemic causes. could be caused.
Crush injuries can cause release of myoglobin into blood damaging kidneys.
not much can be done at maintenance phase. in recovery phase there is a massive output in urine production due to loss of ability to concentrate urine and electrolytes become disturbed.
a
acute tubular necrosis most common cause of renal failure. Toxic causes (endogenous which are native to the body and exogenous which are from elsewhere) and ischaemic causes. could be caused.
Crush injuries can cause release of myoglobin into blood damaging kidneys.
not much can be done at maintenance phase. in recovery phase there is a massive output in urine production due to loss of ability to concentrate urine and electrolytes become disturbed.
acute and chronic tubulointerstitial nephritis (TIN)
causes of TIN include Drugs (until proven otherwise)
TIN is idiosyncratic and not dose related.
drug acts as a hapten combination of tubular protein and the drug that elicits the immune reaction (immune cells in urine and acute renal failure)
acute pyelonephritis is always due to infection whereas TIN is usually drug related
microabscesses in acute pyelonephritis.
treat acute pyelonephritis
d
chronic pyelonephritis
reflux nephropathy is due to damage to valve in causes
das
chronic pyelonephritis presents with coarse irregular corticomedullary scars resemble thyroid tissue and interstitial scarring
asasdas
myelomic kidney is kidney damage caused by multiple myeloma
myeloma is a malignant tumour that causes many symptoms and signs. Kidney injury in many ways. cast nephropathy, amyloidosis, acute tubular necrosis, light chain deposition disease, renal vein thrombosiss
no urine flow through tubul
immunoglobulin is abnormal and huge in numbers and monoclonal. the light chains can be secreted on their own coming out
histology shows fracture lines
amyloid is a type of protein resistant to degradation putting pressure on tissues around them creating atrophy. Beta pleated sheets can be detected by salmon-pink congo red on polarizing LM.
What is hypertensive nephrosclerosis?
2 types:
Benign nephrosclerosis when BP > 140/90 it is due to chronic hypertension.
Most cases of chronic hypertension are caused by primary hypertension.
Malignant hypertension:
Accelerated hypertension which can happen suddenly in an accute manner. BP > 180/110 which causes acute end-organ damage. Third most common cause of renal failure.
What causes secondary hypertension?
Renal factors (renal disease causes hypertension and hypertension causes renal disease it’s a vicious cycle)
endocrine
Cardiovascular
Neurological
Can hypertensive nephrosclerosis cause proteinuria?
Yes it is possible
What is hyalinosis?
Entrapped plasma protein within wall of arterioles
How should malignant hypertensive nephrosclerosis be treated?
As a medical emergency which requires urgent and controlled reduction in BP.
How does malignant hypertensive nephrosclerosis cause disease?
Severe damage to small arteries and arterioles and ischaemic injury to glomeruli and tubules
How does malignant hypertensive nephrosclerosis present?
Acute renal failure and high BP
How should malignant hypertensive nephrosclerosis be treated?
Bring down BP in a slow and controlled fashion to prevent stroke.
What is fibrinoid necrosis?
instead of just hyalinosis there is necrosis of smooth muscle within wall of arteriole and the necrosis resembles fibrin
What is hyperplastic arteriolopathy?
Areteriole can undergo remodelling with smooth muscle proliferating in layers. this is called onion skinning
What is renal artery stenosis?
Uncommon cause of secondary hypertension
What happens during renal artery stenosis?
Usually unilateral critical narrowing of main renal artery causing ischaemic damage to glomeruli and tubules.
Decrease in renal perfusion -> increase in renin secretion -> more AtII -> systemic vasoconstriction -> higher BP
What causes renal artery stenosis?
Atheromatous disease in the elderly and fibromuscular displasia in young women (rarely)
What happens during fibromuscular dysplasia?
fibrous thickiening of intima/media/adventitia of unknown causes. This happens in a beaded pattern.
What are the tubulointerstitial diseases that are relevant to this course?
Acute tubular necrosis
Acure and chronic tubulointerstitial nephritis
Chronic pyelonephritis
Myeloma kidney
How common is acute tubular necrosis?
One of the most common causes of acute renal failure
What are the causes of acute tubular necrosis?
Tubular injury/necrosis can be due to:
Ischaemia (reduced renal perfusion)
Toxins
What causes ischaemic injury to tubules?
Shock, hypovolaemia, vascular compromise
What are the types of toxins that can cause acute tubular necrosis?
Endogenous toxins (myoglobin, haemoglobin, light chains)
Exogenous toxins (drugs, radiocontrast dyes, and heavy metals)
What are the phases of acute tubular necrosis?
Initiation phase (mild oliguria with mild increase in serum creatining)
Maintenance phase (creatinine rises further with uraemia)
Recovery phase (massive diuresis with electrolyte disturbances and hypokalaemia)
What does acute tubular necrosis look like under light microscope?
Dilated tubules lined by attenuated and vacuolated epithelial cells with intrraluminal debris/casts
At the late stage necrosis can be seen with loss of nuclei
In the lumen we can see epithelial cells
What is acute tubulointerstitial nephritis?
Tubulointerstitial inflammation due to various causes.
What are the types of tubulointerstitial nephritis?
Acute and chronic
How does acute tubulointerstitial nephritis present?
Interstitial oedema with neutrophilic/eosinophilic infiltrate
How does chronic tubulointerstitial nephritis present?
Lymphocyte infiltrate with tubular atrophy and interstitial fibrosis
What causes tubulointerstitial nephritis?
Drugs (NSAIDs, PPIs, antibiotics)
Infections (bacteria, viruses, parasites)
Metabolic
Immunological
Vascular disease
Malignancy
Who gets drug related tubulointerstitial nephritis?
It is idiosyncratic and not dose related
How do drugs cause TIN?
Drugs act as a vehicle that combine with components of tubular epithelial cells to elicit immune reaction
What is the clinical presentation of TIN?
Fever
Peripheral eosinophilia
Rash
Mild proteinuria
Eosinophils in urine (in acute TIN)
Lymphocytes in chronic TIN
Acute renal failure
What is the difference between TIN and acute pyelonephritis?
In acute TIN it is usually drug related, inflammation is centered on tubulointerstitial compartment, acute inflammation with tubulitis, and treatment includes withdrawal of offending agent and steroids.
In acute pyelonephritis it is usually due to infection, inflammation is centered on renal calyces, pelvis, and tubulointerstitial compartment, acute inflammation with tubular microabscesses and is treated with antibiotics
What is chronic pyelonephritis?
Chronic inflammation and scarring centered on renal calyces, pelvis, and tubulointerstitium
What are the 2 types of clinical settings in which chronic pyelonephritis is seen?
Reflux nephropathy and obstructive nephropathy
What happens in reflux nephropathy?
Valve between bladder and ureter is defective resulting in retrograde flow during micturition in young children with the congenital defect.and this results in scarring and damage to the tissue
What happens during obstractive nephropathy?
Could be due to any form of obstruction causing buildup of fluid in ureters.
How does chronic pyelonephritis present on the kidneys?
Coarse irregular corticomedullary scars with gross renal calyceal dilation and blunting
How does chronic pyelonephritis present on light microscope?
Chronic tubulointerstitial and pelvicalyceal inflammation with dilated tubules “tubular thyroidisation”
What is myelomic kidney?
Kidney damage caused by plasma cell myeloma
What is a myeloma?
Malignancy of plasma cells with bone lesions, serum paraprotein, kidney injury
What are the renal complications that can result in myelomic kidney?
Cast nephropathy
Amyloidosis
Acute tubular necrosis
Light chain deposition disease
Renal vein thrombosis
What is myeloma cast nephropathy?
A medical emergency that results from intraluminal light chain casts causing renal failure.
What type of antibodies are produced and how do they cause damage in myeloma kidney?
The antibodies that are produced are monoclonal and abnormal because the plasma cells are also abnormal. The light chains are produced separately to heavy chains and they precipitate due to the pH being ideal in the tubules for that. As a result we get kappa or lamda light chain preceipitates
What is the abnormal folding causing myeloma kidney?
AL amyloid or amyloid light chain which accumulates in glomeruli, interstitium and the blood vessels which manifests as severe proteinuria.
What does immunofluorescence show with myeloma kidney?
Kappa or lambda light chains
