Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pathology Term 3 > Week 1 - DM > Flashcards

Week 1 - DM Flashcards

Intro, Pathogenesis, Clinical Pathology, New Developments

1
Q

True or False?

DM = most common lifestyle/NCD

A

True

-in Aus = 7th leading cause of death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the definition of DM?

A

-disorder of metabolism (protein, carb, fat) due to lack of insulin:

T1DM - deficiency
T2DM - resistance * most common

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the characteristic features of DM?

A
  • polyuria
  • polydypsia
  • polyphagia
  • HYPERGLYCEMIA (decr. insulin)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the 2 key consequences of lack of insulin in DM?

A
  1. decreased glucose inside cells
    - cell starving, fatigue, damage and degeneration
  2. increased glucose in blood
    - BV damage (angiopathy) due to oxidation + tissue damage –> insulin = v. oxidative –> kidneys, CNS, eyes
    - immunosuppression (infections increased)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which hormones are involved in blood glucose control?

A

insulin (anabolic) –> decreased glucose (ONLY ONE)

glucagon, glucocorticoids, GH, epinephrine –> increased glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the normal BGL range?

A

3.5-5.5 mmol/L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How does glucose enter cells without insulin?

A

-via GLUT2 receptors into B-cells (insulin-independent)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Outline insulin secretion from B cells in pancreas?

A
  • glucose enters B cells via GLUT2
  • metabolism in mitochondria
  • ATP production results in membrane depol. via K+ secretion
  • Calcium influx results in insulin secretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

True or False?

Liver only has GLUT4 receptors

A

False

-also have GLUT2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Which tissues do insulin act on and what are the functions at each?

A
  1. adipose tissue
    - increased glucose uptake
    - increased lipogenesis
    - decreased lipolysis
  2. skeletal muscle
    - increased glucose uptake
    - increased glycogen synthesis
    - increased protein synthesis
  3. liver
    - increased glycogenesis
    - decreased gluconeogenesis
    - increased lipogenesis

*insulin = ANABOLIC HORMONE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What % of cells in islets of langerhans are B cells?

A

80%

-insulin producing cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the clinical features of DM?

A
  • microangiopathy –> cerebral vascular infarcts, haemorrhage
  • HTN, MI
  • atherosclerosis
  • nephrosclerosis –> glomerulosclerosis, arteriosclerosis, pyelonephritis
  • peripheral vascular atherosclerosis –> gangrene/infarctions
  • peripheral/autonomic neuropathy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Outline primary DM classification

A
  • T1DM (IDDM/juvenile): 5-10%
  • T2DM (NIDDM/adult onset): 90-95%
  • MODY: 5% Maturity Onset Diabetes of Youth
  • LADA: Latent Autoimmune Diabetes in Adults
  • GDM: Gestational Diabetes Mellitus
  • Other: - neonatal diabetes, insulin gene defects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Outline secondary DM classification

A

Excess hyperglycemic stimulus:

  • cushings
  • acromegaly
  • pheochromocytoma
  • steroid Tx.

B cell destruction:

  • pancreatitis/tumours/hemochromatosis (bronze diabetes)
  • infections –> CRS, CMV, TB
  • endocrinopathy, Downs Synd.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are increased infections in DM attributed to?

A
  • BV damage (macro/microangiopathy)
  • glycosylation of chemical mediators
  • ischaemia of tissues
  • lack of inflammatory response
  • increased glucose?
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the 3 etiological factors for T1DM?

A
  1. genetics (HLA DR3/4)
  2. environmental: - virus ?
  3. autoimmunity: - GAD65, ICA512 (against B cells –> insulitis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Outline pathogenesis for T2DM

A
  • genetic predisposition + obesity/lifestyle factors
  • insulin resistance due to adipokines, FFA, inflamm mediators
  • compensatory B cell hyperplasia –> normoglycemia
  • initial increased insulin
  • early B cell failure –> decreased insulin
  • late B cell failure –> DIABETES
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Why is there an initial increase in insulin in T2DM pathogenesis?

A

due to compensatory B cell hyperplasia from insulin resisitance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

True or False?

late stage of T2DM can result in becoming IDDM

A

True

  • total B cell loss can occur
  • normal islets totally replaced by AMYLOID protein
  • pts need to be put on insulin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is proinsulin and what is it broken down to?

A
  • what is released when B cells are stimulated

- broken into C-protein (remains in islets) and mature insulin (secreted)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the difference between T1DM and T2DM with regards to onset of presentation?

A

T1DM:

  • sudden/acute presentation
  • acute attack of hyperglycemia once B cell count falls low enough

T2DM:

  • slow, gradual progression of increased BGLs
  • chronic (yrs)
  • early stages –> asymptomatic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Which type of diabetes are metabolic complications commonest in?

A

T1DM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the chemical mediators of insulin resistance in T2DM?

A
  1. adipokines
  2. inflammatory mediators
  3. FFA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the microscopic feature of islets in T1DM?

A

insulitis –> lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is MODY and which is the commonest subtype?

A

Maturity Onset Diabetes in Youth –> monogenic

  • resembles T2DM but in young pts.
  • 1-6 subtypes
  • MODY2 (glucokinase mutation) = commonest
26
Q

What is type A insulin resistance?

A
  • monogenic
  • hyperglycemia, hyperinsulinemia and insulin resistance
  • insulin receptor mutations
  • acanthosis nigricans
  • females may have PCOS
27
Q

What is LADA?

A

Latent Autoimmune Diabetes in Adults

  • AKA: - 1.5 DM/ Type 3 DM
  • rapid onset, no obesity, difficult control, lack of response to oral Tx.
  • T1DM occuring in late age/adults
  • opposite to MODY
28
Q

Compare T1DM vs. T2DM

A

T1DM:

  • autoimmune dis (gen + env + autoimmune)
  • children <25yrs*
  • IDDM - acute onset
  • acute metabolic complications
  • autoantibody –> YES (GAD65/ICA512)
  • FHx –> no/yes
  • 50% in twins

T2DM:

  • genetic + lifestyle
  • adults >25yrs*
  • NIDDM - slow/chronic
  • chronic vascular complications
  • autoantibody –> NO
  • FHx –> yes
  • 90% in twins
29
Q

What is microscopy of T1DM + T2DM?

A

T1DM:
-islets –> insulitis (lymphocyte infiltrate within islets)

T2DM:
-normal/amyloid (only in late stage)

30
Q

What is the pathogenesis of polyphagia in DM?

A
  • decreased anabolism (decreased insulin)
  • increased catabolism (glucagon, GH, epinephrine) –> increased proteolysis/lipolysis
  • INTRACELLULAR STARVING –> decreased insulin = decreased intracellular glucose –> polyphagia
31
Q

What is the pathogenesis of polyuria and polydypsia in DM?

A
  • decreased insulin/insulin resistance –> hyperglycemia
  • excess glucose filtered in urine (glycosuria) –> takes away increased water in urine with glucose –> polyuria
  • polyuria –> vol. depletion –> polydypsia
32
Q

What are the 3 acute metabolic complications of Diabetes?

A
  1. DKA
    - increase in type 1
  2. HHS/HONK
  3. severe hypoglycemia
    - excess/OD of drugs or insulin OR lack of eating
33
Q

What is DKA and its features?

A
  • increase in T1DM –> acute metabolic complication
  • severe hyperglycemia (increased glucagon/epi)
  • osmotic diuresis and severe dehydration
  • lipolysis, FFA –> ketonemia + ketonuria –> metabolic acidosis + dehydration
  • fatigue, nausea/vomiting (acidosis), Kussmaul breathing (deep + laboured)
34
Q

What is Hyperosmolar Hyperosmotic Synd. (HHS/HONK) and its features?

A
  • severe hyperglycemia (osmotic diuresis + lack of hydration)
  • severe dehydration ONLY (non - ketotic)
  • no acidosis –> therefore no nausea/vomiting/kussmaul breathing
  • common in elderly pts. w DM
35
Q

Why can you get severe hypoglycemia in DM and what are the Sx.?

A
  • excess/OD on drugs or too much insulin
  • lack of eating

Sx: - sweating, palpitations, tachycardia, dizziness/confusion

36
Q

Why do pts. begin losing weight once they develop diabetes?

A

-excess catabolism (lipolysis/proteolysis) + decreased anabolism (decreased insulin)

37
Q

Why are skeletal/striated muscle, adipose tissue and the liver all insulin-dependent tissues?

A

They have GLUT4 receptors on surface which require insulin to transport glucose into cells
*liver also has GLUT2 receptors

38
Q

What are the chronic vascular complications of DM in insulin-dependent tissues?

A
  • striated muscle, fat, liver*

- decreased glucose inside cell –> decreased cell metabolism –> cell starvation

39
Q

What are the chronic vascular complications of DM in insulin independent tissues?

A

BVs, Nerves, Eyes, CNS
-increased glucose in cytoplasm/BVs (hyperglycemia)*

Glucose polymerisation in cytoplasm
-polyols (sorbitol) –> osmotic damage + cell swelling (intracellular)

Activation of protein kinase C
-inflammation, angiogensis, fibrosis –> retinal damage

Glycosylation (glucose combines w body proteins and denatures it)

  • Advanced Glycosylation End products (AGE)
  • AGE deposition in BV wall –> damage –> protein leakage –> thickening (artereosclerosis) –> ischaemia (microangiopathy)

Atherosclerosis (macroangiopathy)

40
Q

What is AGE and what results from it?

A

Advanced Glycosylation End products

  • glycosylation of glucose with body proteins forms AGE (proteins become denatured)
  • AGE deposits in BV wall causing damage, protein leakage, thickening (artereolosclerosis) –> ischaemia (microangiopathy)
41
Q

What is the pathogenesis of microangipathy in Diabetes?

A
  1. hyperglycemia
  2. glycosylation of BM proteins
  3. AGE deposition –> BV wall damage –> protein leakage
  4. increased BM protein deposition (compensatory)
  5. thickening –> hyaline artereolosclerosis from increased AGE deposition
  6. narrowing of lumen –> ischaemia –> BV + organ damage

*microangiopathy = commonest cause of diabetic damage

42
Q

Outline the 2 forms of retinopathy in DM

A
  1. Non-proliferative
    - microaneurysms
    - dots (aneurysms)
    - blots - haemorrhage
    - hard exudates
    - soft/cotton wool –> infarcts
  2. Proliferative
    - neovascularisation
    - larger haemorrhages
    - retinal detachment (geographic areas of haemorrhage + total blindness) :(
43
Q

What is the characteristic damage in DM neuropathy?

A

loss of myelin sheath

44
Q

True or False?

longest nerves are first affected in DM neuropathy

A

True

-distal parts of hand + feet are first affected areas (pins/needles)

45
Q

What are the Sx. of peripheral and visceral neuropathy?

A

Peripheral:

  • bilateral, distal, pins + needles (glove & sock)
  • progressive, irreversible
  • parasthesia, pain
  • muscle atrophy –> late manifestation

Visceral:

  • cranial nerve –> diplopia, Bells palsy (VII)
  • GIT –> constipation/diarrhoea
  • CVS –> orthostatic hypotension
46
Q

What are the features of neuropathic ulcers?

A
  • at pressure points
  • painless
  • surrounded by callus (hyperkeratosis)
  • ‘caved in’/punched out ulcer
  • blood flow NOT affected
47
Q

What is the major cause of morbidity/mortality in DM?

A

Nephropathy

48
Q

What is the pathogenesis of nephropathy in DM?

A
  • hyperglycemia
  • glomerular capillary damage due to protein leakage (microalbuminuria)
  • deposition of AGE in glomerulus –> as a nodule inside loops of capillaries
  • Nodular Glomerulosclerosis (KW lesion) –> compression of capillaries –> decreased blood flow –> eventually diffuse glomerulosclerosis –> End Stage Renal Failure
49
Q

What is nodular glomerulosclerosis AKA?

A

KW lesions

-Kimmelstiel-Wilson Lesions

50
Q

What are diabetic xanthomas?

A
  • reddish/yellow, pruritic, painful lesions/vesicles
  • hyperglycemia + hyperlipidemia
  • subcut. fat necrosis, foamy macrophages + free lipids
  • eruptive xanthoma –> sudden crop of xanthomas (severe)
51
Q

What is the pathogenesis of infections in DM?

A

MULTIFACTORIAL:

  1. impaired inflamm. response –> BV sclerosis
  2. WBC/endothelial damage by glycosylation
  3. glycosylation of chemical mediators of inflammation
  4. decreased metabolism (cell starving)
  5. tissue ischaemia + infarctions –> BV damage (anuerysms/haemorrhage)
  6. increased glucose (alone is NOT the cause)
52
Q

What is the mechanism of cellular damage in insulin-dependent tissues?

A

cell starvation due to decreased glucose entering cells

53
Q

What is the standard first drug of choice for T2DM and what is tis known MOA?

A

Metformin

-decreases hepatic gluconeogenesis

54
Q

What are incretins?

A

GIP –> Glucose dependent Insulinotrophic Polypeptide
GLP-1 –> Glucagon-Like Polypeptide

*function to increase insulin and decrease glucagon

55
Q

What are incretins destroyed by?

A

Dipeptidyl Peptidase (DPP4)

56
Q

What are some new drug therapies used to target incretins?

A

Exenatide –> GLP-1 recpetor agonist (increased incretin function)
…gliptins –> DPP4 inhibitors (decreased destruction of incretins)

57
Q

Which cells secrete incretin hormones?

A

intestinal endocrine cells

58
Q

What are the gross kidney features of a pt. with ESRD following extensive PMHx of T2DM?

A
  • atrophic small kidney
  • cortical atrophy (increased hilar fat)
  • multiple haemorrhagic necrosis areas at renal papillary tips
59
Q

Why is there nodular glomerulosclerosis in glomerulus and not normal arteriolosclerosis?

A
  • foot processes on glomerular capillary surface make it impermeable
  • therefore NO protein leakage possible –> AGE protein deposition remaining inside capillary loop (capillaries pushed to peripheries) –> NODULAR HYALINE GLOMERULOSCLEROSIS
60
Q

What lab. finding is siggestive of initial renal damage in diabetic pts.?

A

microalbuminuria

61
Q

What is the diagnostic microscopic feature of diabetic renal damage?

A

nodular glomerulosclerosis

62
Q

True or False?

epithelial casts in urine is suggestive of tubular damage

A

True

Pathology Term 3 (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions