The fourth stage of diabetic nephropathy has (1) leading eventually to the decreased GFR found in the fifth and final stage.
1. macroalbuminuria, decreased GFR and hypertension
The first stage of diabetic nephropathy consists of (1) and has (2) because of the increased pressure in the (4) which leads to (5) without producing (6) to the nephron
1. hyperfunction 2. hyperfiltration 4. efferent arteriole 5. increased filtration pressure 6. decreased blood flow
Glucose also non-enzymatically reacts with proteins and other molecules to produce (1) products which can activate pattern recognition (2) which activate the innate immune system, causing inflammation, and causing damage to cells and tissues with abundant glycation products.
1. Advanced glycation (AGE) 2. RAGE (receptors for AGE)
Kimmelstiel-Wilson lesions may arise from (1) which are subsequently filled with matrix.
1. aneuysmal dilations of the capillaries
There is also a pathway by which (1) proteins and molecules can stimulate the immune system which leads to destruction and degeneration of cells and tissues with highly (1) molecules.
ANP decreases sodium reabsorption in the (1)
1. proximal tubule
third stage diabetic nephropathy
In all other tissues EXCEPT the kidney, capillary beds have (1) and one side and (2) on the other, which produces a small capillary filtrate that enters the interstitial fluid in the capillary bed (this can be affected somewhat by hydrostatic pressure and oncotic pressure).
1. an arteriole 2. a venule
(1) and its reactions including (2) lead to increased amounts of (3) and can enhance the immune response to increased glucose.
1. Oxidation 2. oxygen free radicals 3. RAGE
Diabetic nephroapthy is in contrast to hypertension which generally only affects the (1). Constriction of only the (1) can raise the hydrostatic pressure, but at the expense of (2)
1. afferent arteriole and not the efferent one 2. reduced blood flow into the glomerulus
The third stage of diabetic nephropathy has a level of (1) in the urine which is not detected by dipstick testing, but can be measured by other approaches and is known as (2)
1. albumin 2. microalbuminuria.
Although less commonly seen than the diffuse lesion, (1) is highly specific for diabetes mellitus and consists of (2) deposits of matrix materials in the absence of nuclei, creating distinct (3) known as (4)
1. nodular glomerulosclerosis 2. nodular 3. anuclear nodules. 4. Kimmelstiel-Wilson lesion
Diabetes can produce renal disease by either macroangiopathy involving (1) or (2) of renal arteries or arterioles, or by microangiopathic disease affecting (3)
1. atherosclerosis 2. hyaline arteriosclerosis 3. capillaries, tubules, or glomeruli
A higher (1) suggests poorer glucose control and more glycation damage in the patient.
1. Hb A1c
The polyol pathway metabolizes glucose into (1) and ultimately (2) which ultimately leads to reduced (3), decreased (4) and impaired (5)
1. sorbitol via aldose reductase 2. fructose via sorbitol dehydrogenase 3. myoinositol 4. Na/K ATPase 5. axonal transport.
Another form of diabetic kidney disease that can be seen is (1) in which entire glomeruli undergo a sclerotic change leading to functional loss since there are ultimately fewer functioning glomeruli.
Because early diabetes constricts the (1) more than the (2) it leads to (3) in the earliest stage.
1. efferent arteriole 2. afferent arteriole 3. greater hydrostatic pressure and filtration rate than normal
(1) generally takes 10-15 years to develop and happens because of deposition of increased (2) in the (3)
1. microangiopathy 2. extracellular matrix proteins 3. glomerular capillary basement membrane and mesangium
The second stage of diabetic nephropathy involves (1) but does not usually have albuminuria.
1. thickened basement membrane and mesangium
Because glycation of proteins is another mechanism which leads to (1), it is useful to have an indicator of the degree of protein modification which occurs in diabetics. (2) is a marker which is used to determine the amount of glucose as well as glycation which has occurred over a period of time as an assay to see how well controlled a diabetic patient’s glucose levels have been over time.
1. hyalinization 2. Glycated hemoglobin or Hemoglobin (Hb) A1c
Histologically the vascular lesions within large arteries consist of (1) changes, whereas the vascular lesions in later stages of diabetes affect both afferent and efferent arterioles producing a (2) deposition of matrix materials from (3) products or a proliferative response within the blood vessel which further occludes the lumen.
1. atherosclerotic 2. hyaline 3. sorbitol or glycation
Increased matrix deposition in microangiopathy occurs as a consequence of (1) which either produce more (2) metabolites or more (3) proteins
1. increased glucose levels 2. glycolytic 3. glycated
Once the GFR falls to low levels, the sympathetic nervous system can directly activate the (1) and increase sodium reabsorption by increasing levels of (2)
1. renin-angiotensin system 2. aldosterone.
Diabetic nephropathy spans several stages between the initial effects which can actually increase (1) and end stage renal disease which requires (2).
1. glomerular filtration rate 2. dialysis or transplant
In the kidney, the glomerular capillary bed is surrounded by (1) on both sides which (2) so that as much as 20% of the (3) is filtered through the glomerulus at any given time.
1. arterioles (afferent and efferent) 2. greatly increases the filtration pressure 3. renal blood flow
thickened basement membrane and mesangium
second stage diabetic nephropathy
first stage diabetic nephropathy
The most common microangiopathic lesion in the glomerulus is a diffuse deposition of matrix materials within the (1), which usually begin at the (2)
1. glomerular capillary basement membrane and mesangium 2. vascular pole of the glomerulus (opposite Bowman’s capsule).
macroalbuminuria, decreased GFR, and hypertension
fourth stage diabetic nephropathy
The deposition in microangiopathy can lead to (1), which disrupts the glomerular filtration barrier leading to (2). This explains the development of (3) in diabetes.
1. fusion of the delicate foot processes within the podocytes 2. proteinuria 3. albuminuria
(1) are also an important contributor to diabetic kidney disease although they can often be subtler and more difficult to detect than the glomerular disease. They are caused by matrix protein deposition within the (2) leading to (3). These changes can extend into the collecting system and (4) is a complication of diabetic kidney disease.
1. Tubular changes 2. tubular cells 3. hyaline (hyaline really means homogeneous) change, necrosis and loss of tubular epithelial cells 4. papillary necrosis
In a similar manner, (1) are activated by stretching of the (2) due to congestive heart failure which increasingly fills the (2) because the left ventricle is too weak to pump out all the blood. In response to this, (3) is produced, which decreases sodium reabsorption in the proximal tubule
1. left atrial baroreceptors 2. left atrium 3. atrial natriuretic peptide (ANP)
Pathogenesis of Glomerular Changes in diabetes:
•Hyperglycemia ↑____ in the glomeruli and of matrix proteins specifically stimulated by this cytokine
•Hyperglycemia also activates _____
•Renal destruction produces _____
TGF-beta; protein kinase C;
HTN (produces further damage)
•Glomerular changes in DM:
•(a) Mesangial expansion induced by 1)
•(b) ↑matrix production of glycosylation of matrix proteins.
•(c) GBM thickening occurs.
•(d) Glomerular sclerosis caused by 2) (ischemic injury from hyaline narrowing of both arterioles).
•RENAL Complication of DM
a and b
•(a) Renal pelvis abscesses
•(b) papillary necrosis.
Tubular lesions hallmark 1) 2)
Hyaline change and EPITHELIAL cell loss (necrosis)
•2) of foot processes
•Increased 3) (makes it more rigid);
Glomerular changes begin in the 4)
1) lamina densa of BM
2)Fusion and loss
4) vascular stalk
•Stages of Diabetic Nephropathy:
•Stage 1: Hyperfunction/hypertrophy ___ due to constriction of the ___.
↑GFR; EFFERENT arteriole;
•Stages of Diabetic Nephropathy:
Stage 2: Silent stage --> thickening of BM and expansion of mesangium; ____ GFR
•Stages of Diabetic Nephropathy:
•Stage 3: Incipient stage --> ___ an GFR begins to ___ . BP will be ↑ in Type 1, while ↑ or normal in Type 2 diabetes.
•Stage 4: Over diabetic nephropathy
_____ decreased GFR and hypertension. *nephrotic syndrome*
Stages of Diabetic Nephropathy
•Stage 5: Uremic --> ESRD and GFR ___; hypertension and albumin excretion is low (since filtration is so low).