Metab Lab Midterm

Labs 1-4

Urinalysis considers what three things

appearance: color and clarity (we expect it to be translucent and straw yellow)

concentration: light (dilute), dark (concentrated)

content: measuring specific compounds

Glucose

• any level of glucose in the urine is indicative of high blood sugar

• GLUT9 and SGLT2 are responsible for reabsorbing all of this glucose in the blood

• however they are saturable

• when they are saturated GLUT9 and SGLT2 becomes escapes in the urine

• the blood glucose concentration at which glucose begins to be observed in the urine is called the renal threshold

renal threshold

the blood glucose concentration at which glucose begins to be observed in the urine

ketone

• when there is insufficient glucose cellular energy production, cells will instead rely on rely on fat oxidation to maintain ATP

• If energy demands are so rapid the TCA cycle cannot keep up w/ energy production, some of the aceytl CoA will instead will be used for ketogenesis and the production of ketones (ketoacids)

pH

• an individuals diet and medications influence urinary pH (which fluctuates throughout the day)

• the presence of acids will lower pH and indicates potential changes that may be natural physiological and metabolic response or indicative of pathology

Why would urine be more acidic in the morning

• this is because when you sleep, your body is in a fasted state, breaking down fats for energy, which leads to ketone body (ketone acid) production

protein

• small amounts of protein can be seen in a healthy individual

• larger amounts of protein in the urine can indicate a multitude of potential issues

  • acute kidney injury or kidney disease

  • proteinuria can occur w/ UTIs, kidney stones, preeclampsia, or even be a temporary response to strenuous exercise

specific gravity

• a measure that compares density or urine to density of water

• low specific gravity indicates dilute urine

• high specific gravity indicates presence of compounds in urine

strengths

• cost effective

• non-invasive

• performed at home

• rapid results

• initial or continual monitoring

• decrease burden on patient, healthcare system

Limitations

• limited scope of assessment

• improper use

• false positive or negatives

• lacks clinical interpretation

• downplay, exaggerate, misinterpret results

• lower accuracy and sensitivity

• rely on color vision

• typically not covered by insurance

Carbohydrate Digestion and Absorption

• Starch is one class of polysaccharides (consist of amylose and amylopectin)

Digestion

• amylase can only digest alpha 1,4

• amylose will be broken down into maltotriose, maltose, and alpha limit dextrins

• the alpha 1,6 bonds of the alpha limit dextrins will be digested by isomaltase to yield maltose and maltotriose

Absorption

• glucose monosaccharides are absorbed from the lumen into the enterocyte by either GLUT2 or SGLT2, then transported into the blood via GLUT2

postprandial

blood glucose changes after a meal

How does blood glucose change during the day

carbohydrates are consumed and absorbed into the blood, resulting in an increase in blood glucose levels

when blood glucose drops, glycogen in the liver will be broken down and released into the blood increasing blood glucose

what is the normal post prandial range

100-140 mg

what is normal fasting blood glucose

70-100 mg

hypoglycemia

below 70 mg

hyperglycemia

above 140 mg/d

Hormonal Regulation

• insulin is released when blood glucose is high

• insulin triggers uptake of glucose from the blood in the cell

• glucose in cells can be used for energy or in the liver and skeletal muscle glucose can also be stored as glycogen

• as a result blood glucose decreases

• glucagon is released from pancreatic alpha cells

• Glucagon helps to increase blood glucose by signaling the liver to break down glycogen to release glucose that can then be released to the blood. Additionally, glucagon will signal cells to use fats (and protein) as a fuel source instead of glucose, which helps to preserve the glucose in the blood for tissues like the brain and RBCs that need glucose!

Insulin Signaling

GLUT4 is the only GLUT that is insulin dependent. Insulin facilitates glucose entry into cells by telling the cells to put GLUT4 transporters into the cellular membrane, which is accomplished by the following steps:

• Pancreatic β cells “sense” the elevated blood glucose

• The β cells release insulin

• Insulin binds to the insulin receptor on a target cell

• Binding activates cellular signaling that causes GLUT4 transporters (stored in GLUT storage vesicles or GSV) to be translocated and inserted into the membrane

• Glucose is taken from the blood into the cell

• Cells use glucose for metabolism!

Type 1 Diabetes Mellitus

• Juvenile or insulin dependent

• caused by beta cells not producing enough insulin (usually because the body’s immune system attacked and damaged/destroyed them)

Type 2 DM

• adult onset or insulin resistance

• not limited to adults

• caused by the body down regulating the number of insulin receptors on the cells

• this is usually in response to the person having chronically high levels of glucose and insulin for awhile

• this loss of insulin receptors is why it is called insulin resistance

gestational diabetes

occurs in some pregnant women because of changes in metabolism during pregnancy

• essentially the mother becomes insulin resistant to ensure that developing fetus gets enough glucose

• controlling blood glucose during pregnancy is very important as failure to do so can lead to birth defects

• gestational diabetes generally resolves on its own but does increase the mothers risk for for developing T2DM

Diabetes Insipidus

• caused by failure of kidneys to reabsorb water

• When it is secreted into the blood, ADH travels to the kidneys and signals the kidneys to conserve water.

• In diabetes insipidus, the there could be issues where the brain doesn't make or release ADH or the problem could be that the kidney doesn't respond to the ADH.

• Regardless, this failure results in large amounts of water being lost in the urine.

glycemic load

(glycemic index/100)/gdGHO

glycemic index

(GI test)/(GI reference)