2. Innovation Team
1- Arterial supply of suprarenal gland and their origins
:
They are 6 arteries supplying suprarenal gland
a. Superior suprarenal artery (Rt, Lt)
Origin: from inferior splenic artery from abdominal aorta
b. Middle suprarenal artery (Rt, Lt)
Origin: from abdominal aorta directly
c. Inferior suprarenal artery (Rt, Lt)
Origin: From renal arteries which originate from abdominal
aorta
2- 3 drugs inhibiting the conversion from T4 TO T3:
1. Propranolol
2. Propyl thiouracil
3. Cortisol
3- Mechanism of action and side effects of
mithemazole
Mechanism of action:
1. Reduce formation of thyroid hormones by inhibiting
thyroid peroxidase
2. Block I2 organification and incorporation into organic
form
3. Inhibit coupling of iodotyrosine to form T3&T4
3. Innovation Team
SIDE EFFECTS:
1. Papular skin rash
2. Lymphadenopathy
3. Leucopoenia, agranulocytosis, aplastic anemia
4. Thyroid enlargement
4- Discuss metabolism (catabolism) of insulin
a. Insulin anabolism:
Gene for insulin synthesis is located in the short arm of
chromosome no.11
Insulin is synthesized as preproinsulin going from N terminal
to C terminal as prepeptide, B chain, C peptide, A chain
the prepeptide is formed of 23 A.A and act to direct the
molecule into the cisternae of the endoplasmic reticulum
then it is removed by proteolytic enzyme.
This result in proinsulin (B chain, C peptide, A chain) that
provide the conformation necessary to for disulfide bridge.
b. Catabolism of insulin
This involves two enzyme systems:
The 1st: insulin specific protease; insulin molecule is cleaved
proteolytically between A.A 16& 17 of B chain
The 2nd: hepatic glutathione insulin transhydrogenase; this
enzyme reduce the disulfide bonds and then the individual
A&B chain are rapidly degraded
4. Innovation Team
5- Role of PTH in phosphate metabolism:
It act to increase dissolution of bone matrix phosphate is
released with calcium but PTH increase phosphate
clearance this the net effect of PTH is to increase
extracellular fluid concentration of Ca+2 and decrease
phosphate concentration
6- The cell that secrete glucagon, site, histological
features
Cell: Alpha cells of islets of Langerhans
Site: it is present on the peripheral part of islets of
Langerhans in pancreas
FEATURES: they are large cells less numerous and about
20% they has small numerous homogenous granules
5. Innovation Team
7- Types of Chromophils, PAS stain, size, secretory
granules
Acidophils Basophils
Size Small Large
PAS stain -ve +ve
secretory
granules
Large Small
Secretion of
granules
1-Somatotrophs
(growth h.)
2-Mammotrophs
(prolactin)
1-Thyrotrophs
(TSH)
2-Gonadotrophs
(FSH& LH)
3-Corticotrophs
(ACTH)
8- Functions of the ADH
1. ADH action on the kidney:
It act on the distal part of DCT, collecting duct and
tubules increasing water reabsorption through increase
water channels formation so cause urine concentration
and decrease its volume.
6. Innovation Team
2. ADH action on BVS:
It is a potent VC that act on vascular smooth muscle
In moderate concentration it has a very potent effect
of constricting the arterioles causing increase in the
arterial pressure
Under normal condition this action doesn't
significantly alter the ABP because it is counteracted
by the baroreceptor reflex
ADH is important in maintenance of ABP in
hypotensive conditions as hemorrhage
9- Metabolic action of thyroid hormone and effects on
CVS:
A. ACTION ON FAT:
They increase all aspect of fat metabolism, mobilization,
synthesis and utilization
They accelerate the oxidation of free FA(this lipolytic
effect is more enhanced that the lipogenic effect
They lower cholesterol, phospholipid and TGs in the
blood.
B. ACTION ON PROTEINS:
a. If small dose: thyroid hormone increases the rate of
formation of proteins by ribosomes and increase RNA
synthesis.
b. If large dose: leads to excess catabolism of the muscles
C. ACTION ON CHO
It increase the rate of absorption of glucose from GIT
after carbohydrate meals and so blood glucose level
increase but it falls again when it is utilized
7. Innovation Team
It enhance gluconeogenesis
D. ON METABOLIC RATE:
They increase the metabolic rate and oxygen
consumption of almost all tissues in the body. The basal
metabolic rate can increase as much as 60 to 100% above
normal when large quantities of the hormone is secreted
E. Increase synthesis of many cellular enzymes :
They increase Na+k+ ATPase and so increase the transport
of both sodium and potassium this process increase the
utilization of energy and heat production so help in
increasing basal metabolic rate
F. ON MITOCHONDORIA:
They increase the number, size and activity so increase
the energy production
g. action on carotene:
It is necessary for the hepatic conversion of carotene into
vit A
Effect on CVS:
Thyroid hormone increase number and affinity of B-
adrenergic receptors on the heart and increase its
sensitivity tocatecholamine which increase all properities
of the heart
Increase the metabolism in tissues cause more rapid
utilization of oxygen and metabolic end products causing
VD this increase the blood flow to the skin for heat
elimination
8. Innovation Team
Increase in blood flow cause increase in venous return
and COP so systolic blood pressure increase but VD causes
decrease in diastolic BP so PP increased
10. Hormones that regulate blood glucose level, and
their function:
GH
1. It decreases the number of insulin receptors
2. It decreases the utilization of glucose by the cell
3. It cause hyperglycemia in high doses
4. It decreases the use of glucose for energy
5. It increases glycogen deposition the glucose that does
enter the cells is rapidly transformed into glycogen
CATECHOLAMINE
They act to increase glucose concentration (fight and flight)
to brain and muscles
CORTISOL
1- It increase the mobilization of amino-acids from extra
hepatic tissue to undergo gluconeogenesis in the liver
2- It decrease glucose utilization by the cells
3- It depresses glucose transport to the cells
4- It has anti insulin effect
5- It cause hyperglycemia
GLUCAGON:
9. Innovation Team
It increase glucose concentration through increasing
glycogenlysis and gluconeogenesis
THYROID HORMONE
It increase the rate of absorption of glucose from GIT
after carbohydrate meals and so blood glucose level
increase but it falls again when it is utilized
It enhance gluconeogenesis
INSULINE
It is glucose lowering enzyme that act to increase entry of
glucose to the cell
It facilitate glycogen synthesis by increasing the activity of
the enzymes needed
Decrease gluconeogenesis through decrease the
quantities and activity of the hepatic enzymes needed
Decrease lipolysis
11- 4 favorable prognosis factors for papillary
carcinoma:
1. Female sex
2. Age less than 20 years
3. The presence of carcinoma in the thyroid gland only
4. Well differentiated histological appearance
12- Renal complications of diabetes:
10. Innovation Team
Renal failure is the second cause of death after myocardial
infarction; it may be present in the form of:
Glomerular lesion:
Diffuse thickening and increase leakage of the basement
membrane of the glomerular capillaries associated with diffuse
or nodular glomeruloscelerosis
Hyaline arteriolosclerosis
Affecting both afferent and efferent renal arterioles
Renal artery sclerosis also occur
Pyelonephritis
Both acute and chronic pyelonephritis are common in
diabetic patient than other population
Necrotizing papillitis is noticed
12. Innovation Team
1- VEINOUS DRAINING OF THYROID GLAND AND
THEIR TERMINATION:
There are 6 veins draining thyroid gland:
a. Superior thyroid vein right and left
Right – right internal jugular vein
Left – left internal jugular vein
b. Middle thyroid vein right and left:
Right – right internal jugular vein
Left – left internal jugular vein
c. Inferior thyroid veins right and left
Both of them join together and pass anterior to the
thyroid to drain into left innominate vein
2- NAME THE CELL THAT SECRETE PTH AND
DESCRIBE IT HISTOLOGICALLY
The cell that secretes PTH is chief cell of parathyroid
gland.
Histologically:
By LM:
Cells are small polygonal more numerous.
Large vesicular nuclei.
Their cytoplasm is pale slightly acidophilic and
granular.
By EM:
13. Innovation Team
The cells showing secretory granules and feature of
polypeptide secretory cells
Moderate amount of organelles rER, Golgi,
mitochondria with lamellar cristae
There are many lipid and glycogen droplets
responsible for pale cytoplasm
3- DIFFERENCES BETWEEN BETA AND ALPHA CELL
OF ISLET OF LANGERHANS
ALPHA CELL BETA CELL
SITE Peripheral Central
SIZE Larger, less
numerous forming
about 20%
Small, Large
number forming
about 70%
STAINING
by
Gomori
stain
Red
(MINTIONED IN
PPT)
Deep basophilic
(MINTIONED IN
PPT)
EM *Large cell
*Numerous
secretory granules
*Have
homogenous
dense core
*Small cell
*Granules have
polyhedral
crystalline
dense core
surrounded by
wide electron
lucent halo
14. Innovation Team
4- Hormones act on the kidney and their functions
3. GH: increase synthesis of erythropoiesis and decrease
Na and Ca excretion in urine.
4. ADH act on the distal part of DCT, collecting duct and
tubules increasing water reabsorption through increase
water channels formation so cause urine concentration
and decrease its volume
5. PTH: IT acts on the kidney causing increase Ca
reabsorption at the level of DCT and increase
phosphate excretion by decreasing its reabsorption at
the PCT
6. Calcitonin: it cause Ca phosphate and magnesium
excretion and it also inhibit synthesis of 1, 25 DHCC
7. 1, 25 DHCC: It facilitates Ca reabsorption in the distal
part of the nephron of the kidney
8. Catecholamine: it cause VC of renal artery causing
decrease urine volume
9. Aldosterone: increase sodium reabsorption in
exchange with excretion of Na + AND H+ in DCT, CD,
CT and it also increase Na+K+ so act to increase Na
and decrease K.
15. Innovation Team
5- Compare between metabolic action of GH and
cortisol
GH cortisol
On
proteins
IT IS AN ANABOLIC
HORMONE
1. It act to increase A.A
transport to inside
the cell so cause
increasing its
concentration
2. It increases the
protein synthesis by
direct effect on
ribosomes
3. It stimulates
transcription of DNA
and increase RNA
causing increase
protein synthesis
4. It decreases the
catabolism of
proteins and A.A
IT IS A CATABOLIC
HORMONE IN
EXTRAHEPATIC TISSUE AND
ANAPOLIC IN THE LIVER
1. It reduce cellular protein in
all body cells except those
of the liver by decreasing
synthesis and increase
catabolism
2. It increase plasma
proteins and liver proteins
3. It increase blood A.A
4. It increase the rate of
deamination of A.A
(INCREASEGLUCONEOGENESIS)
5. Increase protein synthesis
in the liver
On fat 1. It has lipolytic effects
and cause increase
utilization of fat
2. In tissue it enhances
the conversion of FA to
acetyl co.A for energy
production
a. Direct effect: it increases the
mobilization of FA from
adipose tissue, increase their
concentration in the plasma
causing their utilization as
source of energy
16. Innovation Team
b. Indirect effect : through
increase the lipolytic effect of
catechol amines
On CHO 6. It decreases the
number of insulin
receptors
7. It decreases the
utilization of glucose
by the cell
8. It cause
hyperglycemia in
high doses
9. It decreases the use
of glucose for
energy
10. It increases
glycogen deposition
the glucose that
does enter the cells
is rapidly
transformed into
glycogen
6- It increase the mobilization
of amino-acids from extra
hepatic tissue to undergo
gluconeogenesis in the liver
7- It decrease glucose
utilization by the cells
8- It depresses glucose
transport to the cells
9- It has anti insulin effect
10- It cause hyperglycemia
11- Regulation of thyroid gland secretion:
1. Hypothalamic regulation
Stimulation of the hypothalamus causes increase
secretion of THRH which is transported through
hypothalamic hypophyseal portal circulation causing
the activation of anterior pituitary to secrete TSH
Hypothalamus can also cause inhibition of the
anterior pituitary through secretion of Somatostatin
2. Pituitary regulation
Pituitary gland secrete TSH which is responsible
for the activation of thyroid gland to secret T3, T4
17. Innovation Team
3. Negative feedback:
Increased level of T3, T4 cause inhibition the
secretion of hypothalamus and pituitary (mainly)
4. cold : cause acute increase in TSH
5. Stress and anxiety : decreased TSH
6. Blood iodine level:
Adequate dietary iodine intake is important for
normal thyroid function
When intake decreases synthesis and secretion of
iodine decreases and TSH production increase
leading to thyroid enlargement (goiter)
12- Function and clinical significance of C peptide:
Function:
It provides the conformation necessary to for disulfide
bond formation.
Clinical significance:
Peripheral C peptide estimation reflects the rate of
endogenous insulin secretion provided that the kidney
function is normal
C peptide is used to assess pancreatic graft endocrine
function as increase C peptide/ glucose ratio indicate
normal graft function
Serum C peptide is a major indication in hypoglycemia
in insulinoma which is associated with C peptide
increase
18. Innovation Team
Function of 1,25 DHCC:
IT ACT AS A REGULATOR of metabolism of calcium and
phosphorus by promoting the transport of calcium and
phosphate
A. In the intestine:
It induces synthesis of specific mRNA responsible for
synthesis of intestinal calcium binding protein and so
increase the absorption of Ca and phosphate
B. In the bone
It promote bone resorption (mobilization of Ca from
bones)
C.In the kidney
It enhances the reabsorption of filtered tubular
phosphate
13- 4 characteristic features of medullary thyroid
carcinoma:
1- It is neuroendocrine neoplasm originate from
parafollicular C cells
2- Associated with multiple endocrine syndrome IN 20%
3- Amyloid stroma seen in 50% of cases
4- Associated with diarrhea due to calcitonin or VIP
19. Innovation Team
14- CVS complications of diabetes:
It is associated with atherosclerosis and its complications
as:
Myocardial infarction: caused by atherosclerosis of
coronary artery and it is the most common cause of
death
Gangrene: of lower limb 100 time more in diabetic
patient
Hypertension and CVS accidents caused by hyaline
arteriolosclerosis
Diabetic microangiopathy diffuse thickening of the
basement membrane of the capillaries on of the
constant morphological features of DM; CAPILLARIES
IS MOR LEAKY TO PLASMA PROTEINS.
15- Mechanism of action and side effects of
mithemazole
Mechanism of action:
4. Reduce formation of thyroid hormones by inhibiting
thyroid peroxidase
5. Block I2 organification and incorporation into organic
form
6. Inhibit coupling of iodotyrosine to form T3&T4
SIDE EFFECTS:
5. Papular skin rash
6. Lymphadenopathy
7. Leucopoenia, agranulocytosis, aplastic anemia
8. Thyroid enlargement
20. Innovation Team
16- comparison
MRTFORMINGLIBECLAMIDE
4-6 hrs if short acting
24 hrs if long acting
28-24 HrsDURATION
kidneyliverMetabolism
↑ G uptake by tissues
↑ binding to insulin
receptors
↓ G absorption
↓ Hepatic gluconeogenesis
Potent hypoglycemic
↑ G uptake by tissues
↑ binding to insulin receptors
Sensitization of beta cells
Reduction of glucagone
MECHANISM
OF ACTION
1- Type 2 DM with SU if
failed alone
2- Obese diabetics
(appetite suppressor)
3- Metabolic syndrome
(obese)
4- Polycystic ovary:
insulin resistance in ovary
when ↑ insulin binding ,
normal
type 2 DM , prolonged use
will lead to beta exhaustion
& further need insulin
USES
21. Innovation Team
1- GIT upset & metallic
taste
2- Lactic Acidosis
3- Vit B12 , folate
deficiency
Give injection or take Vit &
drug at diff. times
1- GIT upset
2- Hypoglycemia
3- Hypersensitivity
reaction to sulpha
4- Hypothyroidism
(similar to thiouracil)
Bone marrow depression
S.E
1- Renal insufficiency
2- Pregnancy
3- Alcoholics
4- Cardiopulmonary
insufficiency
Hepatic dysfunctionC.I
LOSSGAINWEIGHT
23. Innovation Team
1-It extends from the fifth cervical vertebra to the
first thoracic.
Posterior relations
Isthmus : related to second , third and fourth
tracheal rings.
Its upper border related to the anastomotic artery
between right and left superior thyroid arteries.
Its lower border gives origin to the inferior thyroid
veins.
Lobe:
- upper and lower parathyroid glends.
- Inferior thyroid artery.
- Carotid sheath and its contents.
- Longus coli muscle.
2-Relations of pituitary gland:
Superiorly: related to diaphragm sellae which
separates it from optic chiasma.
Anteriorly: related to the tuberculum sellae and
sphenoidal air sinus which separate it from the
cavity of the nose.
Posteriorly: it is related to the dorsum sellae
which separates it from the pons and basilar
artery
24. Innovation Team
.
3-Follicular cells .
By EM we can see:
Large pale central nucleus ,supranuclear well
developed Golgi apparatus , Extensive rough
endoplasmic reticulum and secretory granules all
of them correlate with protein synthesis.
Also, there is lysosomes in the apical part and the
luminal border shows few microvilli and
endocytotic vesicles for hydrolysis of
thyroglobulin stored in the follicles to be secreted
into the circulation.
4-A- Zona glomerulosa.
B- Zona fasiculata
c- Zona reticularis.
Histological features of Zona glomerulosa:
-It represents about 15% of the adrenal cortex
and it lies directly under the capsule of the gland.
- Cells are arranged in closely packed arched
clusters surrounding fenestrated capillaries.
- Cells are columnar or pyramidal with dense
nuclei and pale slightly acidophilic vacuolated
cytoplasm.
By EM it has the same features of steroid
secreting cells : sER, lipid droplets and
25. Innovation Team
Mitochondriae with tubular cristae.
5-Effects of thyroid hormones on nervous system:
In infants , it is necessary for normal
development of the nervous system , myelination
of the neurons and establishment of normal
synapses.
In adults , it increases the sensitivity of nervous
system to catecholamines and it increases
activation of reticular activating system.
26. Innovation Team
6-Role of Parathormone in calcium homeostasis:
When blood calcium level is decreased PTH is
released to restore the blood calcium level to its
normal level by exerting its effects on:
Bone: it has direct effect on bone by increasing
bone resorption and it includes 2 phases:
Rapid phase: in which activation of the existing
osteoclasts takes place.
Slow phase: in which formation of new
osteoclasts takes place.
Kidney: it increases calcium reabsorption from
the distal convoluted tubules , collecting tubules
and collecting ducts and decreases phosphate
reabsorption from the proximal convoluted
tubules.
Intestine: indirect effect, as it induces 1 alpha
hydroxylase enzyme in the kidney which
increases the active form of Vit.D which
enhances calcium and phosphate reabsorption
from intestine.
27. Innovation Team
7-Insulin and cortisol effects on protein metabolism:
Insulin Cortisol
_ active transport of
many amino acids into
the cell
_ direct effect on
ribosome to increase
mRNA translation so
forming new proteins
_ inhibit protein
catabolism
_ in liver , decrease
gluconeogenesis so
conserve aminoacids
in protein stores in
body
-It has catabolic effect
on protein in all body
tissues except the liver,
it has anabolic effect.
-it increases liver protein
and plasma proteins.
- it mobilizes aminoacids
to the liver from other
tissues, to cause :
-hepatic
gluconeogenesis.
- hepatic protein
synthesis.
- hepatic plasma
synthesis.
8-Causes of hypoglycemia:
a-Overdose of insulin in treatment.
b-Insulinoma.
c- Hypoactivity of thyroids , pituitary and adrenal
glands.
d-Impaired absorption of glucose.
28. Innovation Team
e-Rapid evacuation of food.
9-Mechanism of action of PTH :
It is considered as one of the group IIa hormones
which bind to plasma membrane receptor then
activate a second messanger which is adenyl
cyclase enzyme and then through protein kinase
enzyme some reactions occur.
Its functions:
It increases blood calcium level and decreases
blood phosphate level through:
- On Bone : it increases bone resorption.
- On kidney: it increases calcium reabsorption in
distal convoluted tubules and decreases
phosphate reabsorption in the proximal
convoluted tubule.
- On intestine : it increases absorption of both
calcium and phosphate through its activation of
Vit.D.
29. Innovation Team
10- Thyroid adenomas according to secretory
activity : Non-functioning adenoma , functional
adenoma or toxic.
According to microscopic appearance :
- Trabecular adenoma.
- Microfollicular adenoma.
- Normofollicular adenoma.
- Macrofollicular adenoma.
- Hurthle cell adenoma.
11- Diabetic nephropathy : renal failure is second
to myocardial infarction , characterised by 3
important lesions :
A ) Glomerular lesions : diffuse thickening and
increase leakage of the basement membrane of
glomerular capillaries with diffuse or nodular
glomerulosclerosis
B ) Hyaline arteriolosclerosis : affect afferent and
efferent arteriolosclerosis and renal artery
C ) Pyelonephritis
30. Innovation Team
12- 2 different drugs used for treatment of
osteoporosis:
Calcitonin – Bisphosphonate ( alendronate)
Calcitonin: it inhibits osteoclastic activity and so
inhibit bone resorption.
Alendronate concentrates at the sites of bone
remodeling and induces: - inhibition of
osteoclastic proton pump.
- Inhibition of osteoclastic formation and activity.
- Induction of osteoclastic apoptosis.
13- 1- rapid or short acting + NPH
2-- rapid or short acting + glargine or
detemir
**But we aren't sure concerning it.
