Renal Disease Flashcards by David Houghton

There are the 4 types of renal disease, what is a disease of the glomerula?

disease that affects the filtration capabilities of the kidney

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There are the 4 types of renal disease, what is a tubulointerstitial compartment?

disease affecting the tubules directly or the interstital space

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There are the 4 types of renal disease, what is arcuate blood vessels within the kidneys disease?

disease affecting the arcuate blood vessels
arc like blood vessels run around the medulla

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There are the 4 types of renal disease, what are congenital diseases of kidneys?

inherited kidney disease

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if acute kidney disease always cause chronic kidney disease if left untreated?

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What is the most serious cause of acute kidney disease?

acute glomerulonephritis (acute nephritis)
inflammation of glomerulus

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Acute thrombotic microangiopathy is a cause of acute kidney disease, what is it?

condition where thrombosis in capillaries and arterioles of kidneys is present
can occlude the blood vessels

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Tubulointerstitial nephritis is an acute kidney disease, what is it?

ubulointerstitial nephritis is inflammation that affects the tubules of the kidneys and the tissues that surround them (interstitial tissue).

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What is the most common cause of chronic kidney disease?

diabetes

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Hypertensive glomerulopathy is the second most common cause of chronic kidney disease, what is it?

kidney f disease attributed to a history of hypertension

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What are the 2 main things that are not filtered by the golerulus?

1 - lipid bound drugs

2 - proteins

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What is ultrafiltrate?

what has been filtered in the glomerula

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Ultrafiltrate is what has been filtered in the glomerula. Once filtered where does the ultrafiltrate go?

enters the bowmans capsule (empty space)

then enters the proximal conveluted tubule

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The image below is a cross section of a glomerula. What do each of the acronyms in the image below denote?

JGA = Juxta glomerular apparatus
MD = Macula densa
GBM = Glomerular basement membrane
EPI = Epithelial cell
E = Endothelial cell
BS = Bowman Space
EA = Efferent Arteriole
AA = Afferent Arteriole

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What is the main role of macula densa cells in the proximal conveluted tubules?

provides tubulur feedback on Na+ levels

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The macula densa cells in the proximal conveluted tubules provides tubulur feedback on Na+ levels. If the Na+ levels drop, what 2 roles can macula densa cells perform?

dilate afferent and constrict efferent arterioles
signal to the juxtaglomerular cells to secrete renin

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What is the histology image of below?

normal glomerula with surrounding tubules

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What does the location of immune deposits in the glomerula tell us?

potential histopathological diagnosis

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The image below denotes the different layers of the glomerula, with the acronyms as follows.

GBM: Glomerular Basement Membrane

EN: Endothelial cells

EP: Epithelial cells

MC: Mesangial cells

MM: Mesangial matrix

The location of where immune deposits can be found are numbered 1-5. What do the numbers 1-5 denote?

1 and 2 = Sub epithelial
3 = Sub endothelial
4 = Mesangial
5 = Deposits within glomerular basement membrane

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If the podocytes are damaged in the glomerula, what happens to the filtration?

podocytes normally only allow small positively charged ions to pass
if damaged positive and negative charged ions can diffuse

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If normal podocytes large and negative molecules are unable to pass the podocytes and are therefore not filtered. What is a large negatively charged molecules in the blood that does not not normally get filtered, but if the podocytes are damaged may be able to?

proteins

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Does a high protein in your urine affect urine volume?

no
does not affect urine osmolarity

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In urine microscopy, what is the most important cast?

RBC casts
indicate glomerula disease
bleeding of the glomerula

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What is nephritic syndrome?

clinical name given to a collection of different signs and symptoms
these occur as a result of inflammation in the kidneys

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What is nephrotic syndrome?

- clinical term to describe large amounts of protein that leak into the urine - symprtoms include swelling of body tissues and a greater chance of catching infections

Nephritic syndrome is a clinical name given to a collection of different signs and symptoms that can occur as a result of inflammation in the kidneys. What common features are present with nephritic syndrome?

- heamaturia (RBC casts) - patients have hypertension - acute kidney injury - oliguria (less than 400 ml per day) - proteinuria (usually \< 3.5 g/day)

Nephrotic syndrome is a clinical to describe large amounts of protein that leak into the urine, causing symptoms including swelling of body tissues and a greater chance of catching infections. What other clinical features will they have?

- severe Proteinuria (\>3.5g/day) - serum hypoalbuminemia (\<30 g/L) - generalised oedema - hyperlipidaemia (protein leak causing increased lipoprotein production) - increased risk of venous thromboembolism (loss of anticoagulants)

There are autoimmune diseases that can cause kidney disease. Are there any type 1 hypersensitivity causes of kidney disease?

- IgE response - no known renal disease

There are autoimmune diseases that can cause kidney disease. Type 2 hypersensitivity, which is cytoxic hypersensitivity. Here IgG and IgM antibodies bind to host tissue and identify it for programmed cell death by the complement system, antibody-dependent cell-mediated cytotoxicity (ADCC) where natural killer cells destroy host cells and opspnisation. What renal disease can this cause?

- membranous glomerulonephritis - Anti GBM disease - ANCA associated glomerulonephritis/polyangitis - antibody mediated graft rejection

There are autoimmune diseases that can cause kidney disease. Type 3 hypersensitivity, which is where there are mutliple antibodies bound to an antigen, but the immune cells cannot degrade them. They can then collect in different parts of the body where immune cells can aggregate in an attempt to destroy them. What renal disease can this cause?

- antibody-antigen complexes collect in the glomerulus causing damage - lupus nephritis - post-infectious glomerulonephritis - hepatitis B,C associated glomerulonephritis - cryoglobulinemic glomerulonephritis

There are autoimmune diseases that can cause kidney disease. Type 4 hypersensitivity, which is T cell mediated macrophage and inflammation. CD8+ T cell mediated direct cell cytotoxicity. What renal disease can this cause?

- sarcoidosis - systemic sclerosis related tubulointerstitial nephritis - acute graft rejection

There are 2 main groups of glomerula disease, what are these groups?

1 - primary glomerular disease 2 - systemic disease causing a secondary glomerular injury

There are 2 main groups of glomerula disease, primary glomerular disease and systemic disease causing a secondary glomerular injury. What are the 2 most important diseases?

- minimal change disease - primary membranous glomerulonephritis

There are 2 main groups of glomerula disease, primary glomerular disease and systemic disease causing a secondary glomerular injury. 2 important primary diseases are minimal change disease and primary membranous glomerulonephritis. What is minimal change disease?

- large amounts of protein is lost in the urine - one of the most common causes of the nephrotic syndrome worldwide.

- kidney-specific, autoimmune glomerular disease - presents with increased protein in the urine associated with a pathognomonic pattern of injury in glomeruli

There are 2 main groups of glomerula disease, primary glomerular disease and systemic disease causing a secondary glomerular injury. What are the 2 most common systemic disease causing a secondary glomerular injury?

- diabetes - hypertension

How is glomerular disease diagnosed?

- renal biospy is taken then perform: - light microscopy (LM) - immunohistochemistry (IHC) - electron microscopy (EM)

In diabetic glomerulosclerosis, when a renal biopsy is taken, lesions can be identified, what is the name of these lesions?

- Kimmelsteil Wilson lesions

What is thombotic microangiopathy?

- micro-angio-pathy = small blood vessels disease of kidneys - blood clots can form in body and become thrombotic in blood vessels, causing blockages - in the kidneys these can block and damage micro blood vessels

Thombotic microangiopathy is vascular disease of the kidneys. What can cause this?

- haemolytic uremic syndrome - thombotic microangiopathy - uncontrolled hypertension - antiphospholipid syndrome

There are a number of hereditary nephritis. The most important one for us is Alports syndrome, what is this?

- X linked recessive genetic disorder causing abnormal lamina in kidney - glomerulus basement membrane doesnt filter effectively - causes kidney disease in men, not really women

Alports syndrome is a form of hereditary nephritis, is this more common in men or women?

- can affect both but mainly men - men can have end stage renal disease by 35

What is acute interstitial nephritis?

- inflammation of the interstitial space around the tubules of the kidneys - indicated to be a type 4 hypersensitivity reaction

What can cause acute tubulointerstitial nephritis?

- inflammation - allergies (drug induced) - autoimmune disease (sarcoidosis) - transplant rejection - acute tubular necrosis

What is autosomal dominant polycystic kidney disease (ADPKD)?

- inherited condition causing fluid-filled sacs called cysts to develop in the kidney - kidney function is impaired

What is acute kidney injury?

- damage to the kidney lasting less than 3 months - reduces the filtration of urine

Pre-renal acute kidney injury (AKI) is due to low blood supply to the kidneys. What are the most common causes of low blood supply which result in acute AKI?

- sudden or severe reduction in BP - blockage of blood to kidenys (stenosis)

Renal acute kidney injury (AKI) is damage directly to the kidney cells. What are the most common causes of renal AKI?

- inflammation - infection - drugs - autoimmune disease

Post-renal acute kidney injury (AKI) is an obstruction to urine flow out of the kidney cells. What are the most common causes of post-renal AKI?

- benign prostate hyperplasia - kidney stones - bladder injury/tumour

What is acute glomerulonephritis?

- acute inflammation of the glomerula

A common secondary cause of acute glomerulonephritis (inflammation of the glomerula) is systemic lupus erythematosus, what is this?

- lupus refers to immune system attacking host cells - erythematosus refers to reddening of the skin - autoimmune disease

A common secondary cause of acute glomerulonephritis (inflammation of the glomerula) is the autoimmune disease systemic lupus erythematosus which is caused by a type III hypersensitivity. What is type III hypersensitivity and what tissues does it affect the most?

- formation of antigen-antibody complexes (AAC) - as AACs are in the blood this affects anywhere blood is filtered

A common secondary cause of acute glomerulonephritis (inflammation of the glomerula) is the autoimmune disease systemic lupus erythematosus (SLE) which is caused by a type III hypersensitivity which is the formation of antigen-antibody complexes that can block and damage tissues, causing inflammation. Tissues and organs that filter blood are heavily affected. What does SLE do to the kidney?

- glomerula inflammation damages epithelium, glomerula basement membrane and podocytes - blood is filtered and found in the urine - protein is filter and found in the urine - high BP (electrolytes dont get filtered)

A common cause of acute kidney injury (AKI) is acute tubular necrosis. What is this?

- death of cells in the tubules of the nepheron

A common secondary cause of acute kidney injury (AKI) is acute interstitial nephritis. What is this?

- inflammation of the interstitial space surrounding the tubules and capillaries

A common secondary cause of acute kidney injury (AKI) is acute interstitial nephritis, which is inflammation of the interstitla space surrounding the tubules and capillaries. What are the 2 most common causes of this?

- allergies - infection

A common cause of acute kidney injury (AKI) is problems with the vascular system of the kidneys. What can be the major causes of this?

- vascular dysfunction causing contraction of the afferent arterioles - adhesion of inflammatory cells such as neutrophils

In acute kidney injury (AKI) what will we expect to see on clinical measures?

- reduced GFR (not super acute though) - decreased urine output (oliguria) - increased urea and **_creatinine_** (main one)

In acute kidney injury (AKI) what structural changes can we expect to see in the kidneys?

- cell death (apoptosis/necrosis) - loss of cell adhesion causing a blockage

Nephrotic syndrome is a group of disorders that causes the kidneys to leak large amounts of protein into the urine, but what is happening inside the kidneys to cause this?

- damage to the glomeruls, specifically the podocytes - damaged or no podocytes means large negative proteins can pass through, causing severe proteinuria (\>3.5g/day)

- frothy due to proteins

- hypoalbuminemia (\<30 g/L) - genralised oedema due to reduced osmotic pressure

Nephrotic syndrome is a group of disorders that causes ths kidneys to leak large amounts of protein into the urine. This is caused by damage to the glomeruls, specifically the podocytes, where negatively charged proteins, which were previously unable to pass can now do so. This can cause severe proteinuria (\>3.5g/day). If there are a lot of proteins leaving the blood such as albumin this can cause hypoalbuminemia (\<30 g/L) and genralised oedema due to reduced osmotic pressure. What other marker in the blood can this cause that is produced by the liver?

- hyperlipidaemia

Nephrotic syndrome is a group of disorders that causes ths kidneys to leak large amounts of protein into the urine. This is caused by damage to the glomeruls, specifically the podocytes, where negatively charged proteins, which were previously unable to pass can now do so. This can cause severe proteinuria (\>3.5g/day). If there are a lot of proteins leaving the blood such as albumin this can cause hypoalbuminemia (\<30 g/L)and genralised oedema due to reduced osmotic pressure. If lots of proteins are being lost, one important protein that is lost is anti-thrombin III. Why is this important and what can this cause?

- anti-thrombin III inhibits the coagulation cascade - patients at increased risk of venous thromboembolism

Nephritic sybdrome is a group of disorders that are caused by antigen-antibody complexes (AAC) (type III hypersensitivity) inside the glomerulus. This in turn causes what to happen?

- AACs infiltrate glomerula and block capillaries - WBCs are recruited caused inflammation - inflammation damages the glomerulus basement membrane - blood and protein can leak into urine

Nephritic sybdrome is a group of disorders that are caused by antigen-antibody complexes (AAC) (type III hypersensitivity) inside the glomerulus. AACs can block capillaries, causing infiltration of WBCs which then causes inflammation. The inflammation then damages the glomerula, specifically glomerulus basement membrane (epithelial cells). What are the 3 main things that can then leak out into the urine?

- RBCs causing Heamaturia (RBC casts) - WBCs from tissue injury - protein (mild proteinuria \<3.5g/day)

Nephritic sybdrome is a group of disorders that are caused by antigen-antibody complexes (AAC) (type III hypersensitivity) inside the glomerulus. AACs can block capillaries, causing infiltration of WBCs which then causes inflammation. The inflammation then damages the glomerula, specifically glomerulus basement membrane (epithelial cells). The glomerula is unable to filter as much filtrate meaning what is reduced?

- urine output - presents as oliguria

Nephritic sybdrome is a group of disorders that are caused by antigen-antibody complexes (AAC) (type III hypersensitivity) inside the glomerulus. AACs can block capillaries, causing infiltration of WBCs which then causes inflammation. The inflammation then damages the glomerula, specifically glomerulus basement membrane (epithelial cells). The glomerula is unable to filter as much filtrate causing oliguria (reduced urine output). What can this then cause due to low filtration?

- high BP - low filtration means BP is high due to electrolytes not getting filtered

What is the most common disease causing primary glomerular diseases resulting in nephrotic syndrome?

- minimal change disease

Minimal change disease is the most common disease causing primary glomerular diseases, is this a nephrotic or nephritic syndrome?

- a nephrotic syndrome - no inflammation or blood in urine is the determining factor

What is diabetic glomerulosclerosis?

- damage and scarring of small blood vessels in glomerulus - most common cause of end stage kidney disease - generally presents as nephrotic syndrome

Diabetic glomerulosclerosis is damage and scarring of small blood vessels in glomerulus and is the most common cause of end stage kidney disease, generally presenting as nephrotic syndrome. This has a common signature on bioosy H&E staining, what is this?

- nodular glomerulosclerosis - call Kimmelstiel and Wilson nodules

Hypertensive nephropathy is kidney failure that is caused by a history of hypertension and is the second most common cause of end stage renal disease. What occurs to the kidney in hypertensive nephropathy?

- high BP = thickening of blood vessels - thickened blood vessesl reduces blood flow to afferent arterioles - GFR is then reduced

- macula densa cells in proximal conveluted tubules send low Na+ - juxtamegular cells signalled to released renin activating the RAAS which inturn increases BP - increases BP due to RAAS in a hpertensive patient can then further thicken blood vessels and narrowing and artherosclerosis in the glomerula

Hypertensive nephropathy is kidney failure that is caused by a history of hypertension and is the second most common cause of end stage renal disease. Hypertensive nephropathy causes a thickening of blood vessels which reduces blood flow to afferent arterioles and then reduces GFR. The macula densa cells in proximal conveluted tubules sense low Na+ and signal the juxtamegular cells that release renin activating the RAAS. RAAS makes blood vessels thicker and narrowing, reducing blood flow and leads to artherosclerosis in the glomerula. What then happens to the glomerula?

- ischaemic injury and nepheron death

In hypertensive nephropathy what can we expect to see in patients urine?

- Haematuria with variable proteinuria

- type IV hypersensitivity - T cell mediated response

Acute Tubulointerstitial disease is where the interstitial space surrounding the tubules is damaged due to infiltration with neutrophils and esinophils resulting in inflammation. This is a type IV hypersensitivity T cell mediated response. What can we expect to see urine wise in these patients?

- elevated WBCs - low urine output (oliguria)

- fever - rash

Acute Tubulointerstitial disease is where the interstitial space surrounding the tubules is damaged due to infiltration with neutrophils and esinophils resulting in inflammation. This is a type IV hypersensitivity T cell mediated response. This can cause oliguria (low urine output), increased WBCs in urine and patients can have a fever and rash. What are the most common causes of this?

- infection: acute pyelonephritis - drug allergy (NSAIDS, PPI, antibiotics - autoimmune diseases - sarcoidosis - transplant rejection - acute tubular necrosis

Autosomal dominant polycystic kidney disease (ADPKD) is an autosomal dominat disease, meaning one non sex chromosome is sufficient to develop the disease. What does this disease do to the kidneys?

- hundreds of fluid filled cysts form on the kidneys - cycts collect on tubules and swell making kidneys grow

Autosomal dominant polycystic kidney disease (ADPKD) is an autosomal dominat disease, meaning one non sex chromosome is sufficient to develop the disease. ADPKD causes hundreds of fluid filled cysts to form on the tubules of the kidneys making them swell and making the kidneys grow. What can large cycts do to neighbouring nepherons blood supply?

- impair the blood supply activating RAAS - hypertension follows

Autosomal dominant polycystic kidney disease (ADPKD) is an autosomal dominat disease, meaning one non sex chromosome is sufficient to develop the disease. ADPKD causes hundreds of fluid filled cysts to form on the tubules of the kidneys making them swell and making the kidneys grow. The cysts can also block collecting tubules and lead to what?

- urinary stasis - kidney stone formation

Autosomal dominant polycystic kidney disease (ADPKD) is an autosomal dominat disease, meaning one non sex chromosome is sufficient to develop the disease. ADPKD causes hundreds of fluid filled cysts to form on the tubules of the kidneys making them swell and making the kidneys grow. What can this cause in the urine as the kidneys begin to fail?

- haematuria

Autosomal dominant polycystic kidney disease (ADPKD) is an autosomal dominat disease, meaning one non sex chromosome is sufficient to develop the disease. ADPKD causes hundreds of fluid filled cysts to form on the tubules of the kidneys making them swell and making the kidneys grow. As the disease progresses this can lead to loss of parenchymal tissue of the kidney and cause a specific type of pain, what is this?

- flank pain - discomfort in your upper abdomen or back and sides

- polycystic kidney disease-1 (PKD-1) gene - PKD-1 gene produces a transmembrane protein

Autosomal dominant polycystic kidney disease (ADPKD) is an autosomal dominat disease, meaning one non sex chromosome is sufficient to develop the disease. ADPKD causes hundreds of fluid filled cysts to form on the tubules of the kidneys making them swell and making the kidneys grow. In addition to have a significant effect on the kidneys, what other organs in the body can be affected?

- liver cysts - berry aneurysms of circle of willis (brain) - mitral valve prolapse - colonic diverticula