Flashcards in diabetes Deck (49):
difference betweenDKA and HHS?
DKA - absolute insulin deficiency
- generally lower blood glucose levels
- lipolysis and ketogenesis
- 3-6 L water deficiet
- plasma Na usually normal
- younger patients
HHS- relative insulin deficiency
- blood glucose levels often higher
- often absent lipolysis and ketogenesis
- 8-10L water deficiet
- plasma sodium high
what does the thyroid gland develop as?
an endodermal downgrowth ( thyroglossal duct). the foramen caecum at the back of the tongue marks the site of the down growth.
what shape is the epithelium in inactive follicles ?
simple ,low cuboidal or squamous
What hormone regulates the activity of the thyroid gland and where is it produced?
THYROID STIMULATING HORMONE FROM ADENOHYPOPHYSIS
Which cell organelle produces the protein part of thyroglobulin?
rough endoplasmic reticulum
where is the sugar component added to thyroglobulin ?
the golgi apparatus
Which enzyme, synthesized by the follicle cell, enables iodide to be converted to iodine?
The enzyme phosphofructokinase (PFK1) is a key regulator of glycolysis. Which of the molecule directly inhibits PFK1 activity?
What does glucagon do?
It reduces glycolysis by inhibiting phosphofructokinase
Which enzyme is activated by insulin in skeletal muscle after a meal?
what is the role of calcium ?
structural - teeth bone
neuromuscular - muscle contraction , neurotransmitter release
enzymatic - coagulation factor coenzyme
signalling - intracellular messenger
how much calcium is excreted in urine and faecesin 24 hrs
20mmol /24 hrs in faeces
what 3 different forms is calcium present in serum?
bound to albumin 46%
free ions 47%
complexed with citrate and phosphate
what is the normal range for total serum calcium?
what alters the concentration of Ca2+
changes in H+ and pH
what happens to calcium during alkalosis ?
H+ dissociates from albumin and calcium binding to albumin increases which results in a decrease of free calcium conc. this can produce signs of hypocalcaemia even though the total serum calcium concs are not altered . in acute acidosis the reverse is true.
what is plasma calcium controlled by?
the action of two hormones; parathyroid hormone and 1,25 dihydroxycholecalciferol (calcitriol)
what is PTH?
a polypeptide secreted from the parathyroid glands in response to a decrease in the plasma concentration of free Ca2+ and this change is sensed by a specific Ca2+ sensing protein in the cell membrane of the parathyroidglands
How does PTH act to increase the plasma Ca2+ concentration?
-stimulation of bone resorption , resulting in the release of calcium phosphate
- enhancement of intestinal Ca2+ and phosphate absorption by promoting the formation within the kidney of calcitrol , the major active metabolite of vit D
- increased active renal Ca 2+ reabsorption
do the cells stain differently in the zona glomerulosa and fasiculata
YES- THE CELLS STAIN MORE
DARKLY WITH SMALL DARK GRANULES IN THEIR CYTOPLASM
What is the three-dimensional
organisation of the cells within the zona fasciculata?
RADIAL COLUMNS OF CELLS THROUGH MOST OF THE DEPTH OF THE CORTEX
The cells forming the zona fasciculate appear pale in an H&E stained section and contain
empty looking, small rounded profiles. A name for these is...?
and What has been eluted out of these cells during routine processing for histology?
lipids and cholesterol
what is the approx diameter of fenestrated capillaries ?
What does the term reticularis tell you about the
3D organisation of secretory cells in this part of the suprarenal cortex?
the secretory cells from a 3d network
where does the supra renal medulla recieve blood from first?
the capillaries and sinusoids of the suprarenal cortex ,
second from arterioles passing from the capsule to the medulla
what is the mechanism of orlistat?
inhibition of pancreatic lipase
Where are the insulin receptors?
Tyrosine kinase receptors are found in the liver and striated muscle and adipocytes primarily
Describe glucagon signalling
Glucagon binds to the glucagon receptor
- G- protein coupled receptor
- found in hepatocytes
- increases cyclic AMP
- cAMP stimulates cAMP - dependent protein kinase ( PKA)
Types of insulin deficient diabetes
Insulin resistant diabetes
Metabolic acidosis character
pH is low
HCO3- Is low
CO2 is low
What does leptin do?
Tells hypothalamus about amount of stored fat
What does adiponectin do
Reduced levels of free fatty acids
What does resistin do
Enhances hypothalamic stimulation of glucose production
In normal renal glucose handling 90% of glucose is reabsorbed by
SGLT2 in the PCT
the rest by SGLT1
Commonest disorder of electrolyte balance
What is type 2 diabetes caused by?
Inadequate insulin secretion and peripheral insulin resistance .
What happens in early stages of T2
The response to insulin resistance is to produce more insulin and an increase in insulin secretionby pancreatic beta cells causing hyperinsulinaemia . Beta cells are eventually unable to compensate adequately and blood glucose sugar rises -> hyperglycaemia
What happens when there is too much glucose in the blood
It gets converted to sorbitol via polyol pathway . Sorbitol cannot cross the cell membranes and therefore accumulates inside cells and produces osmotic stresses -> drawing h2o into insulin dependent tissues - there is a build up of ROS and build up of oxidative stress
What medications are insulin sensitisers ?
Biguanides - metformin
Thiazolidindiones - ploglitazone
What medications increase insulin secretion
Sulphonylureas - glibenclamide
Incretin based therapies -
* EXENATIDE mimics GLP1
* SITAGLIPTIN inhibits DPP4
What causes diabetic retinopathy?
Hyperglycaemia causes increased retinal blood flow and disrupts intracellular metabolism in retinal endothelial cells , leading to impaired vascular autoregulation -> increased production of vasoactive substances and endothelial cell proliferation .
Results in capillary hyperperfusion and closure causes chronic retinal ischaemia stimulating growth factors like VEGF that increase vascular permeability - causing retinal leakage and exudation
What is modular diabetic glomerulosclerosis
Thickening of basement membrane and expansion of mesengial cells
Causes of diabetic foot
Due to combo of ischaemia , ulceration and infection
Peripheral neuropathy includes
Charcot foot -change shape of feet
Clawing of toes
Glove and stocking neuropathy
Peripheral vascular disease
Loss of leg hair
Absent pulses cold feet
Proximal artery occlusion
What is vasa nervorum
are small arteries that provide blood supply to peripheral nerves. These vessels supply blood to interior parts of nerves and their coverings.
Reason for diabetic neuropathy?
Occurs secondary to metabolic disturbance , prevalence is related to duration of diabetes and degree of metabolic control.
Examination reveals capillary damage and occulsion of vasa nevorum whcih decreases blood suppply to nerves whcih causes axonal degradation and thickening of Schwann cell basal lamina
Causes impairments in nerve signalling sensory and motor