PBL 5 - Diabetes Complication Flashcards
What class of drugs are (i) enalapril and (ii) losartan?
Angiotensin converting enzyme (ACE) inhibitor.
(ii) Angiotensin 1 (AT1) receptor antagonist .
A frail 80-year-old female with a low creatinine level would be considered
normal, explain why.
Creatinine is the byproduct of muscle metabolism. An elderly female with low
muscle mass would have lower circulating creatinine as a result of reduced
muscle metabolism.
What are the four variables in the MDMR equation integrated in the calculation
of the eGFR?
Concentration of creatinine in blood. Age of the patient .
Sex of the patient. Ethnic origin.
) List the three components of the physical barrier to glomerular filtration. (ii)
The glomerular barrier selects filtrates on the basis of two basic molecular
features: what are they and how does it work?
- Fenestrated capillary endothelium.
- Glomerular basement membrane (GBM)
- Podocytes layer of Bowman’s capsule. [1/2 mark for each]
(ii) size (the diameter of the diaphragm slit excludes big proteins) [1/2] and charge
(negatively charged plasma proteins are repelled by negatively charged proteins of
the GBM AND diaphragm slit AND the endothelial glycocalyx) [1.5 mark].
How can a funduscopy be informative of condition of the patient’s
kidneys in this situation? (ii) Why is it advantageous to use this method?
[2 mark]
Both diabetic nephropathy and retinopathy are caused by Diabetes
Mellitus-related micro blood vessels damage, and the presence and severity of
one reflects that of the other. [1]
(ii) Funduscopy is a non-invasive method (compared to a kidney biopsy) [1]
What kind of diet would you suggest Rena follows to help manage her
diabetes? [1 mark]
Low GI diet
MDRD formula
Modification of Diet in Renal disease (Used to calculate the estimated GFR to check kidney function)
= Serum creatinine, age, ethnicity, gender
What causes podycyturia
Molecular insults (glomerulonephritis/metabolic disturbances) –> contract their actin fibres –> decrease in adherence –> detach after mechanical stress -> BM uncovered.
Layers of the glomerular filtration barrier
o Endothelium of the capillary - Has fenestrae
o Basement membrane – meshwork of collagen and proteoglycan fibrillae w/ gaps
o Epithelial layer (Podocytes) – long foot like processes separated by slit pores
• Endothelial cells, BM proteoglycan and podocytes – negative charges don’t allow plasma proteins through
What is freely filtered through the GFB and what isnt
• Freely filtered – Electrolytes, glucose. Albumin is not – 6nm/ whereas pores are 8 BUT has negative charge and so repulsion by negative charge by negatively charged proteoglycans on BM.
Why does pt have high plasma fasting glucose + glucose in urine
Above the threshold for glucose in the Na/glucose co-transporters that allow reabsorption
Why high HbA1c in plasma
prolonged elevation in plasma glucose (within 120 days) so glucose residues attach to proteins
Why high creatinine
o Freely filtered by the glomerulus under normal conditions
o In glomerular damage – creatinine will accumulate in the body - hypertension
Albumin sits in the gaps so creatinine cannot pass through
Why low albumin in plasma and high albumin in urine
o Albumin is not usually filtered out of the plasma
o With glomerular damage it leaks out
What causes diabetic nephropathy
• Damage of glomerular basement membrane by glomerulo-sclerosis + thickening– glycation of BM – allows albumin to pass
What causes glomerular sclerosis
• Afferent arteriole becomes vasodilated > efferent arteriole –> Increases intraglomerular filtration pressure –> damages glomerular capillaries (increased shearing forces) –> Mesangial cell hypertrophy + matrix secretion –> Glomerular sclerosis
What is microalbuminaemia
albumin excretion between 30-300mmg over 24hrs or ACR>3mg/mmol
What is Proteinuria
albumin excretion >300mg/day or ACCR >30mg/mmol
Diabetic retinopathy and nephropathy link
o Retinal vessels are visible and can assessable clinically –> can indicate microvascular disease
o T1D: no retinopathy = no nephropathy BUT T2D = nephropathy even w/ no retinopathy
Why should BP in patients with nephropathy be lower
reduce proteinuria + intraglomerular pressure
How does high BP cause nephropathy
- High blood pressure → artery damage (kidneys have bare arteries) –> Causes nephropathy
- Treatment of hypertension improves albuminuria and results in delated onset, 135/85 mmHg or 125/75 mmHg for those with heavy proteinuria is desired.
MoA of ACE-I
Angiotensin converting enzyme inhibitor)
Inhibits conversion of angiotensin I to angiotensin II
Reduces vasoconstriction –> efferent dilation –> reduces intraglomerular pressure
Angiotensin II acts on efferent
Egs of ACE-I
Enalapril
Ramipril
MoA of ARB
Angiotensin II receptor blocker)
o Block the action of angiotensin II
o Blood vessels dilate and blood pressure is reduced
