Flashcards in Liver and Pancreas Deck (80)
What is the main function of the liver?
to maintain plasma glucose levels
What four hormones are secreted from the liver?
4. Insulin-like Growth Factors 1&2 (IGF-1, IGF-2)
Do patients with hypertension exhibit high or low levels of angiotensinogen?
How is angiotensinogen activated to angiotensin II?
1. at the juxtaglomerular cells of the afferent arteriole, low blood pressure and low renal perfusion are sensed.
2. Also sensed at the JG cells are low sodium due to a low GFR and low adenosine secretion
3. these two things stimulate the JGA to secrete renin
4. renin converts angiotensinogen to angiotensin I
5. at the lung ACE converts angiotensin I to angiotensin II.
What does angiotensin II do?
1. increased vasoconstriction in systemic arterioles
2. increase aldosterone secretion (uptake of Na and water, increased secretion of K)
3. increased secretion of ADH
4. Increased Na+ reabsorption at PCT
**all effects work to increase the system blood volume and sodium concentration
What stimulates an increased level of angiotensinogen in the plasma?
1. presence of glucocorticoids (cortisol, aldosterone, corticosterone)
2. thyroid hormones (T3 & T4)
3. presence of estrogens (estrone, estradiole, and estriol)
5. angiotensin II
What organs does aldosterone work on?
kidney, colon and ileum
What makes erythropoietin?
synthesized and secreted by the liver and kidney
What is EPO?
glycoprotein/cytokine that stimulates erythrocyte precursors in bone marrow to being maturing into RBCs (erythrocytes)
Where is the principle site of EPO synthesis in the fetal stages of development (up to 32 weeks)?
the perisinusoidal Ito cells of the liver
What is the principle site of EPO synthesis after fetal development?
in the interstitial fibroblasts in the kidney in close association with peritubular capillaries and tubular epithelial cells
Does the liver still contribute to EPO production in adulthood?
Yes the liver and the kidney contribute, however the kidney is the PRINCIPLE site.
What is HIF-1?
hypoxia-inducible factors that are transcription factors present on the EPO synthesizing cells in the liver and kidney. The amount of HIF-1 regulates how much EPO production takes place. HIF-1 is constitutively produced.
How is EPO production regulated?
On each EPO synthesizing cell in the liver and kidney there are HIF-1's. In situations of hypoxia, there are more HIF-1's present leading to increased rate of production of EPO and eventually more differentiation. In situations of normal O2 or hyperpoxia, less HIF-1 is produced leading to a decreased rate of EPO synthesis and decreased rate of differentiation.
Where does erythropoeitin bind and what does it stimulate?
EpoR on progenitor cells and activates JAK2 cascade. Binding stimulates erythrocyte differentiation.
Where is EpoR found?
1. Bone marrow
2. peripheral/central nerve cells
What are some other biological functions of EPO?
1. brain's response to neuronal injury
2. wound healing
What is the main function of thrombopoietin?
- regulation of the number of platelets in whole blood (normal platelet count is 300,000)
- regulates proliferation and survival of megakaryocytes and differentiation of megakaryocytic into platelets.
What is thrombopoietin (TBO) and where is it made?
- made in the liver parenchymal and sinusoidal endothelial cells, bone marrow stromal cells
- made in the kidney at the PCT
- striated muscle cells
Up to 32 weeks gestation, where are the major sources of TBO?
kidney and the striated muscle
Post gestation, where are the major sites of TBO production?
liver and bone marrow, but some production still takes place in the kidney and the striated muscle
What increases the production of TBO in the liver and bone marrow?
the presence of interleukin 6 (IL-6)
Describe the feedback of TBO?
TBO plasma concentrations is controlled by platelets. In the platelets plasma membrane there is a receptor called the mol receptor (CD110. Once TBO binds this receptor, it is catabolized, thus lowering the plasma concentrations of TBO. ONLY FREE TBO STIMULATES MEGAKARYOCYTES. So, if lots of platelets, don't need anymore differentiation. TBO gets catabolized by platelets at a higher rate meaning less megakaryocytic stimulation and thus less platelet production. The opposite occurs when there are low platelet counts, leading to an increase in megakaryocyte stimulation.
What are the stages of platelet differentiation?
-serial mitotic divisions without cell division
- cytoplasm maturation (increased granules and channels)
4. megakaryocyte sheds platelets into the sinusoids of bone marrow
What is Insulin-Like Growth Factors (1&2)?
are endocrines and target tissues in a paracrine/autocrine fashion
IGF-1: main juvenile and growth promoting factor following gestation
IGF-2: main growth promoting factor during gestation
Where is IGF synthesized?
What stimulates IGF synthesis?
Presence of GH. (hypothalamus releases GHRH, which causes anterior pituitary to release GH which stimulates the liver to produce IGF-1 and 2)
What inhibits IGF synthesis?
1. poor nutrition
2. GH insensitivity or lack of GH receptors
3. failures in the downstream pathway after GH
What does IGF-1 bound to?
IGF-BP (binding proteins). There are 6 different types and approximately 98% of IGF-1 is bound to an IGF-BP.