Renal Physiology VI Flashcards
Reabsorbed urea assists in maintaining the hyperosmotic gradient that exists within the
Renal medullary interstitium
This gradient aids in the formation of concentrated urine, and, medullary urea concentrations ensure that the majority of the filtered load of urea is trapped within the kidneys for
Eventual Elimination
Like the other filtered solutes, lots of urea (approximately 50%) is reabsorbed from the
Proximal tubule
Within the thin descending and ascending limbs, urea is secreted via the
UT2 facilitated transporter
This removes a lot of urea from the interstitium, and because of this, in the collecting tubules the lumenal [urea] approximates
110% of its filtered load
In order to prevent excess washing-out of the medullary interstitium, urea is then reabsorbed from the medullary collecting ducts and back into the renal medullary interstitium; this process is mediated by
UT1 and UT4 facilitated transporters
This whole process describes
Renal urea cycling
Renal urea cycling, along with Na+, supports the hypertonicity of the medullary intersitium that promotes the
Reabsorption of H2O from forming urine
In a healthy person, fasting plasma glucose falls within the range of approximately
75-115 mg/dl
In a healthy person, a two-hour post prandial plasma glucose should not exceed
120 mg/dL
Abnormal elevations in these values indicate the presence of a disorder of carbohydrate metabolism such as
Diabetes Mellitus
Glucagon, epinephrine, cortisol, and GH each increase
PLasma Glucose
Lowers plasma glucose
Insulin
Glucagon, epinephrine, cortisol, GH, and insulin control plasma glucose by which mechanisms?
- ) Breakdown/formation of glycogen
- ) Adipogenesis
- ) Absorption of dietary glucose in GI system
- ) Synthesis of glucose
The process of glucose uptake and storage as glycogen
Glycogenesis
The metabolism of glycogen to yield glucose
Glycogenolysis
The synthesis of glucose from other substrates
Gluconeogenesis
Functionally divided into digestive (exocrine) and endocrine segments because of its dual function
The Pancreas
The pancreas is comprised of which two major types of tissue?
- ) Acini glands (exocrine)
2. ) Islets of Langerhans (endocrine)
The Islets of Langerhans contain three populations of endocrine cells with distinct functions. What are they?
alpha cells, beta cells, and delta cells
Secrete glucagon
Pancreatic alpha cells
Secrete insulin
Pancreatic Beta cells
Secrete somatostatin
Pancreatic delta cells
Insulin is synthesized within
Pancreatic beta cells
Under normal circumstances, insulin is secreted when serum glucose levels exceed approximately
100 mg/dL
Insulin is a storage hormone in that is promotes
Glycogenesis and lipogenesis
Insulin together with GH promotes
Muscle anabolism
Promotes the cellular uptake of serum glucose in the liver, skeletal muscle, and fat
Insulin
Thus, when serum glucose levels rise, insulin production and secretion is
Stimulated
Insulin blocks
Liver gluconeogenesis
Cellular uptake of both K+ and FFA are stimulated by
Insulin
A specific transport protein located within the plasma membrane of B cells that facilitates the movement of glucose into the B cells
Glucose transporter-2 (GLUT-2)
Within the B cells, glucose is phosphorylated by glucokinase, and this results in the formation of
Glucose-6-phosphate (G-6-P)
Intracellular ATP concentrations rise and ATP-sensitive K+ channels are phosphorylated in response ot the formation of
G-6-P
This causes closure of the ATP-sensitive K+ channels resulting in
Cell depolarization
Depolarization causes voltage-gated Ca2+ channels to open. The subsequent elevation in intracellular Ca2+ activates the
Secretory granule machinery
Circulates in bioactive form and activates it’s specific cell surface receptor in target cells
Insulin
Activation of insulin is coupled to the activation of glucose carrier proteins which results in the
Rapid influx of glucose by facilitated diffusion
Insulin promotes the uptake, storage, and utilization of glucose by the
Liver
Insulin also inhibits liver
Gluconeogeneis and glycogenolysis
The predominant source of sustaining blood glucose during fasting periods via gluconeogenesis and glycogenolysis
Liver
Begins with the diffusion of glucose into hepatic cells
Glycogenesis
Once in the cells, glucose is rapidly phosphorylated by glucokinase, thus forming
G-6-P
The conversion of glucose into G-6-P is important because G-6-P can not
LEve the cells
Serves as the intermediate that can be further metabolized for glycogen synthesis
G-6-P
Additionally, G-6-P serves as an entry intermediate into biochemical pathways that enable the production of
ATP
In addition to being expressed with hepatocytes, glucokinase is produced within
Pancreatic B cells
Glucose dependent glucokinase activity mediates the secretion of
Insulin
The major site of post prandial glucose disposal
Skeletal muscle
Provides the substrate for the production of ATP in skeletal muscle
Glucose
Uses glucose (from glycogen stores) and FFA for the production of the vast quantities of ATP that are needed to sustain cross-bridge cycling
Metabolically active skeletal muscle
Activated in response to increased metabolic demand in order to provide increased intracelular glucose for use in the production of ATP
Glycolytic pathway
Insulin is the major hormone that stimulates the synthesis of
-to be stored in adipose tissue
Triglycerides
In adipose tissue, promotes the use of glucose rather than fatty acids for metabolic energy
Insulin
In the liver, insulin stimulates
Fatty acid synthesis
In the liver, insulin augments the conversion of excess glucose into
Fatty acids
In the liver, the synthesis of hepatic triglyceride and lipoprotein are increased in the presence of
Insulin
In skeletal muscle, Insulin suppresses the activity of
-Blocks oxidation of FFAs
Lipoprotein lipase
An anabolic hormone and much of it’s anabolic affect is attributed to it’s effects on protein metabolism, especially in the presence of GH
Insulin
For example, insulin increases the uptake of certain aminos into muscle cells and also can stimulate
Translation
Concomitantly, the catabolism of certain muscle proteins is impaired by
Insulin
What occurs in the absence of insulin from amuscular standpoint?
Increased catabolism, decreased protein synthesis
Insulin secretion declines precipitously when serum glucose levels are
Less than 80-90 mg/dL (i.e. normal fasting concentration)
Thus, when serum glucose is low, insulin secretion is suppressed and for tissues get their energy from
Fat metabolism
A large polypeptide that is secreted by the alpha cells within the islets of Langerhans
Glucagon
Referred to as the hyperglycemic hormone because it induces rapid elevations in serum glucose levels
Glucagon
Glucagon is thought to act exclusively in the
Liver
Within hepatocytes, glucagon stimulates
Glycogenolysis and gluconeogenesis
The pattern for glucagon secretion is inversely proportional to
Serum insulin and glucose levels
Glucagon secretion increases during a fast, when serum glucose levels are below
80-90 mg/dL
Glucagon is especially important in
Neonates
Aids in maintaining the proper level of serum glucose and avoiding extremes in hypoglycemia while babies are learning to break down and extract sugars and other nutrients from milk or formula
GLucagon
A polypeptide secreted by the delta cells within the islets of Langerhans
Somatostatin
In general, levels of somatostatin increase during the
Post-prandial period
Exerts transitory inhibitory effects on insulin and glucagon secretion
Somatostatin
A disturbance in the normal carbohydrate metabolism that results from insulin insufficiency
Diabetes Mellitus
If a patient has a fasting glucose level of higher than 126 mg/dL on 2 occasions, and/oral oral glucose tolerance test greater than 200 mg/dL at two hours on two occasions and or HbA1c gretaer than 6.5 % is classified as
Diabetes Mellitus (DM)
DM is classified as an HbA1c level of greater than
6.5%
HbA1c is essentially just Hb with a
Glucose tacked on
A good indication of glycemic status of a patient within the preceding 8-12 weeks
HbA1c
Diabetes Mellitus has which three main smyptoms?
The three Ps
- ) Polydipsia (thirsty)
- ) Polyuria (peeing a lot)
- ) Polyphagia (ecessive hunger)
Since hyperglycemia increases the filtered load of glucose, more glucose in the forming urine acts as an
Osmotic diuretic (thus polyuria)
Other common sequelae of DM result from complications of microvascular and macrovascular pathology as the disease progresses. These include
Blurred vision, paresthesias, muscle fatigue, and muscle cramps
With severe enough impaired glucose uptake, metabolic demand (i.e. ATP production) cannot be met by glycolysis so instead metabolism shifts from glycolysis to lipolysis resulting in the oxidation of free fatty acids and the formation of
Ketone bodies
Keep in mind that ketoacids in and of themselves are not all bad, they do provide a substrate for
Energy
However, when ketoacid production exceeds that of usage, the accumulation of these acids results in the development of a ketoacidosis known as
Diabetic Ketoacidosis
The broad clinical markers of type 1 DM are
Hypoinsulinemia with hyperglycemia
Type 1 DM is calssified as an
Autoimmune disorder
What are the two subtypes of type 1 DM?
Type 1A and type 1B
Autoimmune in nature and results from the degeneration of pancreatic B cells or the suppression of B cell function due to infiltration by mononuclear/lymphocytic cells
Type 1A DM
Known as idiopathic non-autoimmune diabetes
-less common
Type 1B DM
Type 1 DM is medically managed by
Insulin replacement
The most predominant form of DM, accounting for approximately 90% of DM
Type 2 DM
Insulin resistance appears to precurse the development of impaired glucose tolerance, but rarely progresses to Type 2 DM without some decrement in
B cell function
Predicts the progression from impaired glucose tolerance (IGT) to full on type 2 DM
Elevated FFA
In fact, the effect of insulin on cellular FFA uptake is more profound than its effect on
Glucose uptake
What has a more predominant genetic component, type 1 DM or type 2 DM?
Type 2
results from some defect most likely at the level of the insulin receptor, insulin transport, and/or insulindependent signal transduction, with resultant tissue insensitivity to insulin
Type 2 DM
Type 2 DM is defined by
Insulin insensitivity
Therefore, type 2 is polygenic in nature with combinations in
Insulin resistance and Insulin secretion
Manifests in the major insulin-sensitive tissues, those being skeletal muscle, fat, and to some degree the liver
Insulin resistance
Because the target cells can not effectively respond to insulin, serum insulin levels may be normal or more likely elevated in the face of
Hyperglycemia
