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
Eg of ARB
o Losartan, Candesartan
What is diabetic retinopathy
• Disease of the retina involving damage to the blood vessels in the fundus
What is non-proliferative diabetic retinopathy
Dilation of the retina veins and micro aneurysms which can cause internal haemorrhaging and oedema in the retina
o Oedema in the central retina – main cause of vision loss in this case
o The blood glucose levels in these blood vessels increases and damages pericytes which control blood flow to retina
Proliferative diabetic retinopathy
o Lack of oxygen causes fragile, new blood vessels to form (Bc VEGF) near the optic disk and grow on the vitreous chamber and elsewhere in the retina
o They can bleed – reduce vision – lead to separation + detachment of areas of the retina
o Cotton wool spots, copper wiring
What increases retinopathy in diabetes
Hyperglycaemia increases blood viscocity
Diagnosis of diabetic retinopathy
o Visual acuity test, pupil dilation, fundoscopy
o Look at the retina for signs of leaking blood vessels, retinal swelling, fatty deposits in the retina or changes in blood vessels
Treatment of diabetic retinopathy
o Laser photocoagulation
o Corticosteroids
o Anti-VEGF drugs
What is diabetic neuropathy
• Damage to nerve fibres and blood vessels supplying nerves due to high glucose
Peripheral neuropathy
pain or loss of feeling in arms, feet and legs
Autonomic neuropathy
changes in digestion, bowel and bladder control, erectile dysfunction and the nerves supplying the heart
Proximal neuropathy
pain in thighs and hips and weakness in legs
Focal neuropathy
can affect any nerve in the body and it causes pain or weakness
• 60-70% of people with diabetes develop some sort of nerve disease
