21 - Pathology of the Thyroid II Flashcards
What is diabetic MICROangiopathy?
A small vessel disease leading to hyaline arteriolosclerosis
What is the most common morphologic feature of diabetics with microangiopathy?
- Diffuse thickening of basement membranes ***
- The thickening is most evident in the capillaries of the retina and renal glomeruli
Think RETINA and KIDNEY
Describe the hyaline accumulation
- The basal lamina separating endothelial cells from the surrounding tissue is markedly thickened by concentric layers of hyaline material composed of type IV collagen
Describe the properties of the capillaries
- Despite the increase in the thickness of basement membranes, diabetic capillaries are MORE LEAKY than normal in terms of plasma proteins ***
What diabetic complications does diabetic microangiopathy lead to?
The microangiopathy underlies the development of
- Diabetic nephropathy
- Diabetic retinopathy
- Some forms of neuropathy
How does diabetic microangiopathy effect a diabetic’s legs?
Microangiopathy worsens the ischemia caused by atherosclerosis
This is why many diabetics lose their legs ***
Describe the vessels of diabetic microangiopathy
- High glucose leads to glycosylation
- There is damage to the basement membrane of vessels and they become leaky
- AGEs deposit in the wall of vessels
- This creates a very thick membrane wall and very narrow vessels
- This is especially harmful in the kidneys and eyes but it can happen anywhere
Thick, narrow and leak SMALL blood vessels in the capillaries of the kidneys and eyes ***
What are the long term complications of diabetes mellitus?
- Damage to blood vessels in the kidneys
- Damage to blood vessels in the eyes
- Damage to nerves
- Peripheral vascular disease
- Coronary artery disease
Describe the damage to blood vessels in the kidneys
This can lead to…
- Diabetic nephrosclerosis, including nodular Kimmelstiel-Wilson glomerulopathy
- Pyelonephritis
- Papillary necrosis
Describe the damage to blood vessels in the eyes
Exudative and proliferavitve retinopathy will occur
Describe the damage to nerves that will occur
SYMMETRIC polyneuropathy
Describe the diagnosis of diabetes mellitus
- High fasting glucose or impaired glucose tolerance
- Without diabetes, oral glucose loads cause only a slight rise in blood glucose due to brisk insulin response
- With diabetes, blood glucose rises markedly for a sustained period
What morphological changes will you see in the kidneys of diabetic patients?
- More white, which is excess basement membrane with the deposition of protein
- This will later fibrose and hyaline structures will form
What is a Kimmelstiel-Wilson nodule?
When hyaline structures within the kidney become fibrosed
This is called diffuse glomerulosclerosis
What type of kidney infections are diabetic patients at risk for?
- Pyelonephritis (infection of the renal pelvis)
- Cortical infections of the cortex of the kidney
Describe a pyelonephritis infection
- Gram negative bacilli (E. coli common)
- Causes an infection in the renal pelvis
- The bacteria comes from the urine
- It is a “retrograde” infection
Describe a cortical kidney infection
- Staphylococci infection
- Causes infection in the cortex of the kidney
- The bacteria comes from the blood
What are the three types of neuropathy diabetics can experience?
- Sensory
- Peripheral
- Visceral
Describe sensory neuropathy
Sensory neuropathy can lead to motor neuropathy - problem with myelin
Describe peripheral neuropathy
- BILATERAL and SYMMETRIC ***
- Progressive, irreversible
- Parasthesia, pain, muscle atrophy
Describe visceral neuropathy
- Cranial nerve neuropathy can lead to diplopia and Bell palsy
- GI neuropathy can lead to constipation or diarrhea
- Cardiovascular neuropathy can lead to orthostatic hypotension
What is diabetic MACROangiopathy?
- A large vessel disease
- A process of accelerated atherosclerosis ***
- The problem is nonenzymatic glycosylation of lipoproteins ***
Describe how glycosylation of lipoproteins lead to MACROangiopathy
- LDLs “stick” best to glycosylated collagen
- AGEs (advanced glycation end products) bind to their special receptors in the intima of the vessels and cause the production of fibrous tissues
Describe the detrimental effects of MACROangiopathy
The result of diabetic macroangiopathy is…
- Stroke
- Gangrene of the lower extremities
- Myocardia infarction ***
This will take its toll and will often occur early in life
What can help prevent diabetic macroangiopathy?
Good glycemic control does help the accelerated atherosclerosis, confirming the idea that it’s due largely to the accumulation of AGEs that cause collagen production
Describe the cause and development of neuropathic ulcers
Etiology
- Peripheral sensory neuropathy
- Trauma and deformity
Factors
- Ischemia
- Callus formation
- Edema
Hard to cure - not a regular ulcer
The loss of sensation can lead to SEVERE injury since the patient doesn’t feel any pain ***
Describe diabetic retinopathy
- Ischemia due to microangiopathy and artherosclerosis serves as a stimulus for neovascular proliferation
- These abnormally small cells are prone to hemorrhage
What occurs in diabetic retinopathy?
A constellation of changes in the retina
- Pale area of EDEMA around the central avascular macula
- Numerous small new blood vessels at the periphery of this zone (NEOVASCULARIZATION)
- HEMORRHAGIC FOCI
Describe the clinical differences between type 1 and type 2 diabetes
Type 1
- Onset under 20 years
- Normal weight
- Markedly low blood insulin
- Anti-islet cell antibodies
- Ketoacidosis common (DKA)
Type 2
- Onset over 30, mostly over 40
- Obesity ***
- Blood insulin is normal to moderately decreased late in the disease
- No anti-islet call antibodies
- Ketoacidosis is rare
- Nonketotic hyperosmolar coma ***
Describe the genetic difference between type 1 and type 2 diabetes
Type 1
- 30-70% twin concordance
- Linkage to MHC class II HLA genes
Type 2
- 50-90% concordance in twins
- No HLA linkage
Describe the pathogenesis difference between type 1 and type 2 diabetes
Type 1
- Autoimmune destruction of beta cells mediated by T cells
- ABSOLUTE *** insulin deficiency
Type 2
- Insulin resistance in skeletal muscle, adipose tissue and liver
- Beta cell dysfunction and relative insulin deficiency
Describe the pathology difference between type 1 and type 2 diabetes
Type 1
- Insulitis early
- Market atrophy and fibrosis
- Beta cell depletion
Type 2
- No insulitis ***
- Focal atrophy and amyloid deposition ***
- Mild beta cell depletion
What is the most common underlying cause of diabetic complications?
KNOW THIS
Non-enzymatic glycation of extracellular matrix
is the MOST common underlying cause
in the pathogenesis of complications in DM
Describe pancreatic neuroendocrine tumors (NETs)
- Much less common than adenocarcinomas of the exocrine pancreas
- Accounts for ony 2% of pancreatic neoplasms
- When functioning, they produce distinct clinical syndromes related to the peptide hormone they produce
What are the three most common and distinctive clinical syndromes associated with functioning pancreatic NETs?
1 - Hyperinsulinism (insulinoma)
2 - Hypergastrinemia (Zollinger-Ellison syndrome)
3 - Multiple endocrine neoplsia 1 (MEN 1) syndrome (Wermer syndrome)
He said, “KNOW EVERYTHING about NETs”
What is an insulinoma?
- A beta-cell tumor
- They are the MOST common pancreatic NET
- May be responsible for the elaboration of sufficient insulin to induce clinically significant hypoglycemia
What is the characteristic WHIPPLE TRIAD of insulinomas?
1 - attacks of hypoglycemia that occur with blood glucose levels of less than 45
2 - attacks consist principally of CNS manifestations (confusion, stupor, loss of consciousness)
3 - attacks are preceipitated by fasting or exercise and promptly relieved y food (or IV administration of glucose)
KNOW THE TRIAD ***
Describe the morphology of insulinomas
- Most often found within the pancreas
- Can be found anywhere in the pancreas (head, body, tail)
- Generally benign
- Most are solitary
- Usually small (often less than 2 cm)
- Encapsulated pale nodules
- Look remarkably like “giant islets”
- They are carcinomas (malignant tumors) in only 10% of cases
How are insulinomas described?
- Small circumscribed homogenous tumors
- Uniform cells found in nests
What other cellular structure do we find in insulinomas?
Amyloid is often found in insulinomas
Patients with insulinomas, particularly small ones have excellent prognosis
What is the second type of pancreatic neuroendocrine tumor (NET) we will talk about (and the only other one we will focus on)?
Gastrinomas
Called Zollinger-Ellison syndrome
Describe gastrinomas of Zollinger-Ellison syndrome
- Pancreatic gastrinoma is a neuroendocrine tumor that consists of so-called “G cells” that secrete gastrin
- Patients with Zollinger-Ellison syndrome develop multiple peptic ulcerations in the stomach, duodenum and even jejuum as a result of elevated gastric acid secretion caused by a gastrin-secreting tumor (“gastrinoma”)
Describe the ulcers of patients with Zollinger-Ellison syndrome
- Ulcers are present in almost all patients with Zollinger-Ellison syndrome
- They are identical to the usual peptic ulcerations except that they are often MULTIPLE, found in UNUSUAL LOCATIONS (i.e. jejunum) and may be more difficult to control
What population do we commonly see Zollinger-Ellison syndrome in?
- Gastrinomas are most often found in patients between the ages of 30-50, which a slight male predominance
Describe the behavior of gastrinomas
- Gastrinomas may have a benign behavior, but many are malignant and capable of local invasion and metastasis to the LYMPH NODES and LIVER (more commonly the liver)
Describe the gastrinomas of Zollinger-Ellison syndrome
- Usually a single tumor
- Hypersecretion of gastric acid and multiple severe gastric and duodenal peptic ulcers are present in 90-95% of patients
- When intractable peptic ulcers occur in unusual locations such as the jejunum, Zollinger-Ellison syndrome should be considered
** Commonly missed diagnosed **
Describe the tendency of gastrinomas to metastasize
- Over half of gastinomas are locally invasive or have already metastasized at the time of diagnosis
- Most are low-grade, but the only way to tell is whether it has metastasized
Describe the tendency of gastrinomas to occur with MEN 1 syndrome
- Approximately 25% of cases arise in conjunction with other endocrine tumors
- An example is in MEN 1 syndrome - multiple endocrine neoplasm
- Frequently multifocal
