Islet cell Pathology and suggestive Slides, insulin activity,comparison

1. DR.MOHAN T SHENOY
1st YEAR DM RESIDENT ENDOCRINOLOGY
AIMS- KOCHI
Page 1

2. 1869 German anatomy student Paul Langerhans
first described “islands of clear cells ” distributed
throughout the pancreas but he did not realize the
physiologic significance of these cell clusters, which
are today known as islets of Langerhans.
We now know that islets are the endocrine
compartment of the pancreas, comprising around
2 – 3% of the total pancreatic volume.
Islets are approximately spherical with an average
diameter of 100 – 200 μ m, and a healthy human
pancreas may contain up to a million individual
islets, each having its own complex anatomy,
blood supply and innervation.

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5. 
98% of organ produces digestive enzymes (exocrine)

Composed of acini and ducts

Acini cuboidal to columnar cells with cytoplasmic zymogen
granules

Ducts are lined by columnar epithelium

Fat, alcohol stimulate secretin, cholecystokinin production

These stimulate 2-2.5 liters of alkaline enzyme containing fluid
per day

6. 
Functional definition (Dr. McDonald):
“a group of diseases characterized by high levels of blood
glucose resulting from defects in insulin secretion, insulin
action, or both.”
Pathologic Anatomy:
Chronic hyperglycemia leads to:
1) accelerated atherosclerosis in arteries
2) altered basement membranes in small vessels

RESULT: damage to multiple organs

8. 
LONG-TERM PATHOLOGIC EFFECTS ARE THE
SAME IN BOTH TYPES

These effects are extremely variable and quite
unpredictable for any given patient regarding:
SEVERITY
 DISTRIBUTION
 RATE OF APPEARANCE OVER TIME


Organs affected in addition to pancreas:


Macrovascular disease: accelerated atherosclerosis causes
ischemia of heart, kidneys, brain, lower extremities
Microvascular disease: kidneys, eyes, nerves

11. Primary abnormality: failure of self-tolerance in T
cells

Autoreactive T cells survive ( ? defective clonal deletion in
thymus or failure of regulatory T cells)

T cell activation in peripancreatic lymph nodes and
pancreas, recognizing antigens released from
damaged  cells

Secondary events: development of antibodies


Anti-islet cell
Anti-glutamic acid decarboxylase 65 (GAD 65)

12. 
There are nearly 1 million islets of Langerhans in the normal adult pancreas.
They vary greatly in size from 40 to 900 μm.

Larger islets are located closer to the major arterioles and smaller islets are
embedded more deeply in the parenchyma of the pancreas.

Most islets contain 3000 to 4000 cells - Islets are highly vascularized, and
receive up to 15% of the pancreatic blood supply despite accounting for only
2 – 3% of the total pancreatic mass.

Each islet is served by an arteriolar blood supply that penetrates the mantle to
form a capillary bed in the islet core.

β - cells comprise 60 – 80% of the islet cell population

Islets are well supplied by autonomic nerve fibers and terminals containing
the classic neurotransmitters acetylcholine and norepinephrine, along with a
variety of biologically active neuropeptides.

13. 







1 million 100-200 mm islets total 1-1.5g
5 major types
β cells 70% of cells (Insulin)
α cells 20% of cells (Glucagon)
δ cells (Somatostatin)
Є cells that secrete Ghrelin, and
PP cells that secrete Pancreatic Polypeptide
2 minor cell types: D1 (VIP) & Enterochromaffin cells
(serotonin)
MALLORY-AZAN STAIN
α cells – Brilliant Red
β cells – Orange Brown
δ cells - Blue

14. 
1-2% of body wt (in adults)

5% of body wt (in infants)

Combined wt of all islets = 1-1.58 gm
β cells - More on dorsum and in tail region adj. to spleen

15. 
In humans, β cells generally located in central part,
mostly hererochromatic nature.

Islet cells > 0.4 mm diameter = hypertrophic

Largest cells are centrally located with pink cytoplasm,
larger nuclei, prominent nucleoli and coarse chromatin.

Islet cells are not static
– apoptosis occurs to remove cells
- multiplication by cell division and nesidioblastosis

20. “PEACOCK with PLUMES spread out” – curvilinear arrangement of
glomeruloid islets with hilum and vascular pattern

24. 
Lesions not pathognomonic, generally more severe in type I
than type 2

Both types: Decreased numbers of islets
 Increased islet size and number in infants of mothers with
overt or gestational DM

Type I:
 T-lymphocytic infiltrate/insulitis
 Progressive depletion of  cells -Later small indistinct or absent
islets
 Fibrosis of islets

Type II:
 Amyloidosis of islets
 Ill defined reduction in islet cell mass
 Fibrous tissue accumulation in some islets

25. Islet of Langerhans (black oval) with surviving
islet cells (inside blue shapes) after islet cell
destruction by many infiltrating lymphocytes
Fig. 24-33 A, Robbins
Pathologic Basis of Disease,
8th ed, Elsevier 2010

26. ISLET AMYLOID
A pathologic feature present in 90% of patients with T2DM
is the abnormal extracellular deposits of islet amyloid.
These deposits are localized in the pancreas and are
not part of a systemic amyloidosis disorder.
The islet amyloid is formed from IAPP or amylin, a 37
amino acid peptide.
IAPP is normally produced by the β - cell, stored along
with insulin in its secretory granules, and then co secreted with insulin following β - cell stimulation.
IAPP has no known physiologic function in human

29.  Most
common islet cell
tumor
 5-10%
metastasize
 Presents
with
hypoglycemia (<50mg/dl),
confusion/stupor with
fasting/exercise,
symptoms improve with
food

30. Gritty gray hard masses ; Vast majority are adenocarcinomas, with poorly formed
glands and densely fibrous stroma
Carcinoma of pancreatic head: invasion of ampullary region with bile outflow
obstruction, & distension of biliary tree