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Year 2 Med > U10C6 CKD And Diabetes > Flashcards

U10C6 CKD And Diabetes Flashcards

1
Q

What is the function of exocrine acinar cells?

A

allow digestion of food by releasing pancreatic juice with bicarbonate and enzymes into the pancreatic duct

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2
Q

What are the hormones secretes by the endocrine pancreas?

A

Somatostatin- inhibits glucagon and insulin

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3
Q

How does high blood pressure lead to insulin release?

A
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4
Q

Endogenous insulin synthesis leads to increased blood levels of:

A
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5
Q

What are the anabolic effects of insulin?

A
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6
Q

What is the structure of insulin?

A
  • Insulin has 3 disulfide bonds
  • 2 disulfide bonds connect chain A and B
  • The third disulfide bond is in an intrachain cons in chain A
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7
Q

How is insulin formed?

A
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8
Q

What is the importance of c-peptide?

A

C-peptide is important for folding of the polypeptide and it has a long half life- diagnostic importance to differentiate type 1 and type 2 diabetes

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9
Q

How is insulin secretion regulated?

A

Incretin- GIP and GLP

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10
Q

How is insulin synthesised and released?

A
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11
Q

Where is GLUT2 and GLUT4 located?

A

GLUT-2 (insulin independent) present in liver and pancreas

GLUT-4 (insulin dependent) present in adipose, muscle and heart

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12
Q

What are the target tissues and actions of glucagon?

A
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13
Q

How is the secretion of glucagon regulated?

A
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14
Q

What are the actions of glucagon in the liver, renal cortex and fat cells?

A
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15
Q

What is glucose homestasis?

A
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16
Q

What is the mechanism of the insulin receptor?

A

Tyrosine kinase receptor

Insulin is a hormone that utilizes a tyrosine kinase receptor mechanism for signaling. When insulin binds to its receptor on the cell surface, it induces a conformational change in the receptor. This change activates the receptor’s intrinsic tyrosine kinase activity, leading to the phosphorylation of tyrosine residues on the receptor itself.

The autophosphorylated tyrosine residues on the insulin receptor then serve as docking sites for downstream signaling molecules. These molecules, like insulin receptor substrate proteins (IRS), bind to the phosphorylated tyrosine residues, initiating a signaling cascade. This cascade includes activation of phosphoinositide 3-kinase (PI3K) and Akt pathways, which play crucial roles in regulating glucose uptake, metabolism, and other cellular responses.

In summary, insulin binding to its tyrosine kinase receptor triggers a series of phosphorylation events, ultimately regulating cellular processes essential for glucose homeostasis.

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17
Q

Fasted vs fed state?

A

Fasted- 5-6 hours after meal- glucagon
Fed- 2 hours after meal- insulin

18
Q

What is type 1 diabetes?

A

Can result from atrophy or destruction of b-cells of pancreas due to an immune response or viral infection

19
Q

What is type 2 diabetes and its treatment?

A

insulin resistance - more insulin than normal is needed for the insulin receptors to respond. Subsequent beta cell failure

20
Q

What are the signs and symptoms of diabetes?

A
21
Q

What are the complications of diabetes?

A
22
Q

What are the laboratory tests for diagnosis and long-term management of DM

A
  • Fasting plasma glucose > 126 mg/dL: Screening test - 8 hours after meal
  • Random plasma glucose (>200mg/dL) with one of symptoms v
  • Elevated HbA1c levels >6.5%
  • Oral glucose tolerance test (OGTT)- Evaluates the ability to regulate glucose metabolism. Considered as the gold standard test’. Used to identify patients with ‘prediabetes’ and gestational diabetes. 2-hour plasma glucose >200mg/dL after 75 gms of glucose (OGTT)
23
Q

What is the significance of HbA1c?

A
  • Non-enzymatic glycation of hemoglobin (depends on plasma glucose levels)
    Indicator of long-term glucose control (Over previous 3-4 months)
  • Poor blood glucose control (high HBA1c), higher risk of complications (microvascular and macrovascular)
  • Optimal blood glucose control reduces risk of complications in diabetes
  • Used for diagnosis of diabetes mellitus - greater than 6.5%
24
Q

What is the Pathophysiology of type 1 diabetes?

A

• In type 1 diabetes, T-cells react against poorly defined beta cell antigens (lack of self-tolerance)
• Type IV hypersensitivity response - autoimmune destruction of beta cells –GAD/IA2/ZnT8 antibodies associated
• These mechanisms lead to progressive destruction of the pancreatic beta cells – leading to a loss of insulin release preventing cells from taking up glucose from the bloodstream = emergence of the symptoms of diabetes
• Glucose transporter (GLUT4) is not moved to cell membrane in response to insulin
and cells cannot take up glucose from bloodstream
• lack of glucose in adipose (fat) cells decreases fat synthesis and increases fat
breakdown, and fatty acids released into the blood and oxidised to ketone bodies
• Hyperglycaemia leads to symptoms of diabetes

25
Q

What is the Pathophysiology of type 2 diabetes?

A

• Reduction in peripheral insulin sensitivity or insulin resistance (hyperinsulinaemia) of skeletal
muscle and adipose tissues
• Current hypotheses suggest that insulin resistance might be mediated by either:
• i) Intracellular accumulation of free fatty acids in skeletal muscle and hepatocytes (possibly
via activation of PKC’s which inhibit normal insulin signalling pathways) or
• ii) Endocrine functions of adipocytes- Altered release of resistin, adiponectin and leptin all
favour a reduced sensitivity of target tissues to insulin
• Secondary beta cell failure also seen. Beta cell hyperplasia and hypertrophy occur in the attempt to
make more insulin to reduce blood glucose. Beta cells also secrete amylin which builds and
aggregates in the islets and causes hypoplasia and hypotrophy of beta cells
• Glucose transporter (GLUT4) not moved to cell membrane in response to insulin (insulin resistance)
preventing cells from taking up glucose from the bloodstream as well as failing to inhibit hepatic
gluconeogenesis– therefore hyperglycaemia results
• hyperglycaemia leads to symptoms of diabetes

26
Q

How does poorly controlled diabetes lead to kidney failure?

A

Overview: Insulin deficiency can result in hyperglycaemia which can lead to hypertension and kidney disfunction. Hypertension further exacerbates kidney disfunction and can lead to kidney failure.
For additional information:
Three mechanisms contributing to diabetic nephropathy caused by underlying hyperglycaemia:
1) Increased pressure state. Hypertension = increased pressure throughout arteriovascular system = increased pressure in afferent arteriole which in turn increases the filtration rate of the glomerulus. Efferent vasoconstriction due to activation of RAAS builds up pressure in the glomerulus, increasing filtration rate. Hyperglycaemia also activates RAAS, increasing glomerulus filtration rate
2) Increased pressure results in mesangial expansion – in response to damage, the mesangial cells response by secretion of cytokines that produce inflammation and oxygen free radicals that results in endothelial disfunction. This leads to decreased surface area in the glomerulus for filtration. Dilation of the fenestrations allows larger molecules e.g. proteins to leak out
3) Combination of the above factors lead to nephron ischemia and atrophy of the vasculature which will reduce the kidney’s ability to filter blood, ultimately leading to kidney failure in diabetic nephropathy

27
Q

What is the normal eGFR?

A
28
Q

How is renal function assessed?

A
29
Q

What is diabetic nephropathy?

A
  • Diabetic nephropathy (DN) is a chronic kidney disease defined by structural and functional changes that develop as a result of microvascular complications associated with long-standing or poorly controlled diabetes
  • Diabetic nephropathy is the leading cause of chronic kidney disease (CKD)
  • Major risk factor is hypertension
  • Diabetic nephropathy is a clinical syndrome characterized by:
    ✓ Persistent albuminuria
    ✓ Decline in GFR
    ✓ Raised arterial blood pressure
  • Albuminuria is the first sign and peripheral edema is the first symptom of diabetic nephropathy
30
Q

What is the pathogenesis of diabetic nephropathy?

A
  • Hyperglycaemia leads to the production of reactive oxygen species and activation of pathways (protein kinase C, polyol, hexosamine, and advanced glycation end products (AGE)).
  • Marked inflammation by an increase in cytokines and chemokines, including IL-6, MCP-1, TGF-beta, and VEGF = inflammation fibrosis and increased vascular permeability.
  • Causes podocytopathy, resulting in albuminuria.
  • The resulting systemic and intraglomerular hypertension results in proteinuria.
  • Proteinuria causes epithelial-mesenchymal cell transformation leading to fibroblasts and chronic tubular injury
31
Q

What causes accumulation of AGEs?

A
32
Q

How is glomerular hypertension caused?

A
33
Q

How is tubuloglomerular feedback activated?

A
34
Q

What are the 5 stages of diabetic nephropathy and what are the treatments at each stage?

A

❖ Stage 1 (Very early diabetes/Hyperfiltration)
• Hyperfiltration with increased capillary glomerular pressure
• Above normal Glomerular Filtration Rate (GFR)
• Glomerular hypertrophy / Increase Renal size

❖ Stage 2 (developing/silent stage)
• Continued hyperfiltration and hypertrophy
• GFR remain elevated or return to normal
• No evidence of albuminuria
• Glomerular damage in the form of basement membrane thickening and mesangial expansion

❖ Stage 3 (Microalbuminuria)
• Urinary albumin excretion rate becomes abnormal (e.g., 30–300 mg/24 hr)
• Renal functions could be normal or reduced
• Hypertension develop during this stage

❖ Stage 4 (Overt nephropathy)
• Urinary albumin excretion is more than 300 mg, and creatinine levels in the blood rise
• Majority of patients at this stage have systemic hypertension
• If untreated a vicious cycle of progressive renal impairment develop leading to end stage renal disease

❖ Stage 5 (Uremia)
• GFR has fallen to <15ml/min
• Renal replacement therapy

35
Q

What is the treatment and management for diabetic nephropathy?

A
36
Q

What are the functions of each part of the nephron?

A
37
Q

What are the Pathophysiology of the complications of diabetes?

A
38
Q

What is peritoneal and haemodialysis?

A
39
Q

What are the symptoms and risk factors for CKD?

A
40
Q

What do CKD renal function and blood tests results show?

A

HbA1c high
- HBA1c = glycated haemoglobin (non-enzymatic glycation of Hb - glucose binds to RBCs) - so used as measure of glycaemic control (over previous 3-4 months)
- Normal = <42mmmol/mol (< 5.7%)
- Prediabetic = 42-47mmol/mol (5.7-6.4%)
- Diabetic = >48mmol/mol (> 6.5%)
- Insulin resistance - of liver, skeletal muscle, adipose tissue = no/little response to insulin → dec insulin secretion → cannot respond to hyperglycaemia - do have excess glucose in blood - so get excess binding of glucose to Hb = excess HBA1c

Cholesterol high
- HDL holds the cholesterol it ‘carries’ very strongly - so cholesterol is less able to become loose & attach to arterial walls
- LDL holds the cholesterol it ‘carries’ less strongly - so cholesterol is more able to become loose & attach to arterial walls (so LDL deposits its cholesterol on arterial walls) = forms plaques which can occlude lumen- limiting blood flow = atherosclerosis if partially occludes coronary artery = angina OR fully occludes = MI)
- Dyslipidaemia -> present in diabetics - characterised by hypertriglyceridemia, low HDL, high LDL, high total cholesterol → So is linked to higher risk of cardiovascular complications in diabetics → So TDs are prescribed statins e.g., atorvastatin - to lower cholesterol synthesis

EGFR low
- Measure of creatinine in blood as it is excreted as a waste product from muscles- amount made should equal amount excreted
- Hyperglycaemia
- More NA+ reabsorption to absorb excess glucose
- Less NaCl detected by macula densa in DCT
- RAAS activated
- Increase in BP and renal perfusion
- Angiotensin 2 will cause efferent arteriole constriction
- Pressure increase causes damage to glomerulus

Albumin/creatinine ratio high
- Don’t want albumin in urine but want creatinine
- Ratio is high as there is more albumin and less creatinine

Potassium, urea, phosphate high
- Decreased GFR
- Decreased renal excretion
- Increased resorption

Calcium and 1,25-dihydroxy vitamin D3 low
- Decreased conversion of calcidiol to calcitriol
- Decreased levels of calcitriol in the blood
- Decreased calcium absorption from the small intestine

PTH high
- Hypocalcemia
- Decreased inhibition of PTH release
- Increased PTH in blood

41
Q

What is kidney transplantation?

A

Year 2 Med (60 decks)

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