Exam 2 Flashcards
Liver functions
carbohydrate metabolism, protein metabolism, lipid biosynthesis, storage of important substances, metabolic end-product excretion and detoxification, and bile pigment formation
Carbohydrate metabolism includes
gluconeogenesis and glycogen synthesis
Protein metabolism includes
most serum proteins synthesized in the liver, metabolic pool of amino acids
Lipid biosynthesis
excess carbs turned to fatty acid (palmitate), form ketone bodies, synthesis of VLDL and LDL, form bile acids
Storage of which important substances
iron, glycogen, amino acids, lipids and vitamins
Metabolic end-product excretion and detoxification
bind compound to protein, modify compound by hydroxylation and detoxification
Bile pigment formation
bilirubin and biliverdin
What is jaundice?
yellowish decolorization of skin and sclera from hyperbilirubinemia
Causes of jaundice
increase in bilirubin load on liver, defect in conjugation of bilirubin, defect in secretion of conjugated bilirubin, obstruction of the larger bile ducts
Classifications of jaundice
prehepatic, hepatic, posthepatic, neonatal, kernicterus
Prehepatic jaundice example
hemolytic anemia
hepatic jaundice example
defective conjugation or hepatitis
posthepatic jaundice example
impaired excretion of bilirubin to bile ducts
Neonatal jaundice example
physiological jaundice
Kernicterus
result of deposition of unconjugated bilirubin in nuclei of brain and nerve cells, causing cell destruction and encephalopathy
What is Hepatitis
inflammation of the liver
What causes hepatitis
viruses, bacteria, parasites, radiation, drugs, chemicals or toxins
Which hepatitis’ are caused by viruses?
A, B,C, D, E and CMV
What causes Hep. A?
Hep A virus, fecal-oral route
Hep. A virus
spherical particle containing DNA
Hep A symptoms
non-specific, abnormal ALT with or without jaundice, fecal shedding of the virus
Hep A antigen
not detectable in serum
IgM antigen for HAV
produced in initial phases
IgG antigen for HAV
produced in later phase and lasts years
How common is chronic carrier?
rare
Is there a vaccine for hep A?
Yes, but only available if over 2 years old and traveling or working in area with high transmission
How is Hep B transmitted?
parenteral, perinatal and sexual routes
Hep B virus structure
Central DNA core surrounded by a protein coat
Where is HBcAg?
The core
Where is HBsAg?
on surface
Where is Hep B virus found in the body?
All body fluids
Hep B clinical symptoms
abnormal liver functions tests, variable clinical courses with 2/3 asymptomatic and 1/3 have hepatitis-like syndrome
Recovery for Hep. B?
90% recovered in 6 months and develop antibody to HBsAg, 10% develop chronic hepatitis, cirrhosis, and carcinoma
Vaccine for Hep B?
Nationwide vaccine and immunoglobulin if needle-stick or born to an infected mother
What is tested for in all donated blood?
HBsAg
What is significant about HBsAg?
It is the first serological marker of acute Hep. B infection and can help identify infection before onset of infection
What after HBsAg disappears?
development of anti-HBsAg, common in most of the population
What is HBcAg?
the core antigen found in nuclei of hepatocytes during acute infection, not found in plasma
What develops first, anti-HBsAg or anti-HBcAg?
anti-HBsAg
Which Ig is shown for acute Hep. B infection?
IgM
Is HBcAg in serum?
Yes, it is associated with DNA dependant DNA polymerase so it is detectable in serum
HBeAg
E antigen correlates the number of infectious virus particles and the degree of infectivity of HBsAg-positive sera
What does HBeAg indicate?
unfavorable prognosis and chronic liver disease
Hep B viral DNA assay
nucleic acid hybridization or polymerase chain reactions, a more sensitive measurement of infectivity and disease prognosis, monitor the effectiveness of antiviral therapy in patients with chronic HBV
How is Hep. C transmitted?
the Hep C virus, caused by blood transfusions
What type of virus is Hep C?
an RNA virus
How is HCV detected?
Antibody can detect most infectious patients, but only at later stages, HCV RNA for early detection
HCV antibody
Not protective, can disappear years after infection
HCV symptoms
mild clinical course or asymptomatic
HCV progression
High progression to chronic hepatitis, cirrhosis and carcinoma
Assay for HCV antibody
just a screening test, may have false-positives
What is liver cirrhosis?
The irreversible scarring process by which normal liver is replaced with abnormal nodular structures
Causes of Liver cirrhosis
alcohol abuse, hemochromatosis, postnecrotic cirrhosis, primary biliary cirrhosis, Wilson’s disease, alpha-1-antitrypsin deficiency
What does cirrhosis cause?
portal hypertension, hypoalbuminemia and deficiency of clotting factors
Primary malignant tumors of the liver
carcinoma and hepatoma originating from the liver, related to previous infection with a hepatitis virus, may have elevated alpha-fetoprotein
Secondary tumors of the liver
Metastatic tumor to liver from primary site, more frequent than primary tumors
Reye’s syndrome
Unknown cause, primarily found in children, fatty infiltration of liver with necrosis, cholestasis, and encephalopathy following recovery from viral infection
Drug + alcohol related liver disease
Can cause hepatic necrosis leading to coma and death, may be subclinical, include the use of ethanol, anti-inflammatory drugs, phenothiazines, and antineoplastic agents
Assessment of liver function
Self-reading, Jendrassik-Grof method for total and conjugated bilirubin, urobilinogen in urine and feces, enzyme tests in liver diseases
Pancreas
large gland involved in digestive process, composed of endocrine and exocrine tissue
Endocrine
4 cell types that secrete 4 hormones into the blood, insulin, glucagon, gastrin, and somatostatin
Exocrine
secrete ~ 2 L/day of fluid with digestive enzymes with high concentration of sodium bicarbonate, under both nervous and endocrine control
Secretin
Secreted by mucosal cells in duodenum when acidic contents, causes production of alkaline pancreatic fluid to protect lining of intestines
CCK
produced by cells of intestinal mucosa when fats or amino acids in duodenum, causes release of enzymes from acinar cells by pancreas into pancreatic fluid
Cystic Fibrosis
disease of exocrine function resulting in chronic respiratory infections, pancreatic enzyme insufficiency, and associated complications, autosomal recessive disorder caused by mutations in CF transmembrane conductance regulator (CFTR) gene that controls chloride channel to transport chloride into duct cells
What cells are affected by CF?
cells that produce mucus, sweat, saliva and digestive juices, making secretions thick and sticky, plugging tube, ducts, and passageways
CF causes what to happen?
small and large ducts dilate and convert small cysts filled with mucus, resulting in prevention of pancreatic secretions reaching duodenum or a plug blocking the lumen of bowel, leading to obstruction
How is CF diagnosed?
Elevated chloride concentration in sweat and specific genetic tests
Pancreatic carcinoma
5% of all deaths from malignant neoplasms, 5-year survival after surgery is less than 2%, tumors derived from exocrine tissues, arise as adenocarcinomas of ductal epithelial, present with jaundice, weight loss, anorexia, nausea, and pain
Insulinoma
result of very low blood glucose levels followed by insulin shock
Gastrinoma
AKA Zollinger-Ellison syndrome, watery diarrhea, chronic peptic ulcers, and marked gastric hyper-secretion and hyperacidity
Glucagon-secreting tumors
Can cause diabetes mellitus due to hyper-secretion of glucagon
Pancreatitis
Caused by autodigestion of pancreas from reflux of bile or duodenal contents into the pancreatic duct, acute edema with fluid in retroperitoneal space, necrosis of acinar cells and hemorrhage, intrahepatic and extrahepatic pancreatic fat necrosis
Pancreatitis is associated with
alcohol abuse or biliary tract disease
How is pancreatitis characterized?
increased serum amylase and lipase
Amylase
digesting carbs, only plasma enzyme normally found in urine
Lipase
function in hydrolyzing glycerol esters of long-chain fatty acids, synthesized in the pancreatic cells and secreted to GI, not present in urine, elevated in pancreatitis
Gastric secretions
include release of HCl, gastrin and pepsinogen, respond to neurogenic impulses, distention of stomach, contact of protein breakdown products, and gastrin
What inhibits gastric secretions?
high gastric acidity, inhibitory polypeptide and vasoactive intestinal polypeptide
When do intestinal secretions begin?
when the weakly acidic digestive products and lipids enter duodenum
Intestinal secretions
secrete GI hormones to regulate digestion and absorption so products of carbs, lipids, and proteins are absorbed into blood stream
Gastrointestinal hormones
released by endocrine cells in gut mucosa, influence motility, secretion, digestion and absorption, regulate bile flow and secretion of pancreatic hormones, affect tonicity of vascular walls, blood pressure, and cardiac output
Gastric acid
Determined from the titratable acidities and volumes of the component specimens, used for detection of anacidity and the extreme hypersecretion of gastrin
tests to measure gastrin
used to diagnose Zollinger-Ellison syndrome, fasting gastrin and provocative test, determined by RIA
malabsorption syndrome
impaired absorption of fats, proteins, carbs and other, may result from exocrine pancreas and biliary tract or intestinal diseases
D-Xylose absorption test
urine or serum, differentiating malabsorption from exocrine pancreatic insufficiency
Hydrogen breath test
detect lactose intolerance, measure gases produced in intestinal lumen by breakdown of carbs and diffused into bloodstream
Fecal fat analysis
Qualitative or quantitative, increase is manifestation of malabsorption syndrome, cannot distinguish among types
Sources of fecal fat
unabsorbed lipids, lipids excreted into GI, cells shed into GI, and metabolism of intestinal bacteria
Carbs
compounds containing C, H, and O with a general formula of (CH2O)n and some derivatives like phosphates, sulfates and amines, either aldose or ketose
Digestion and absorption of carbs
digested by salivary alpha-amylase in mouth, then by pancreatic enzymes in small intestine and then by enzymes from intestinal mucosal cells, absorption requires energy and specific transport protein
Embdem-Myerhof pathway
gain 2 moles of ATP and then more from introduction of pyruvate into the TCA cycle and NADH into ETC, important for tissues like muscle that have energy requirements without an adequate oxygen supply
Hexose monophosphate shunt
permit the formation of ribose-5-phosphate and NADPH, preventing cells from free radical damage
Glycogenesis
used for glucose storage
Epinephrine
produce by adrenal gland, released during fight or flight, increase plasma glucose by inhibiting insulin secretion and increasing glycogenolysis and promoting lipolysis
Cortisol
produced by adrenal gland, released on stimulation by adrenocorticotrophic hormone, increase serum plasma glucose by decreasing intestinal entry into the cell and increasing gluconeogenesis and lipolysis
Growth hormone
produced by anterior pituitary, released on stimulation by decreased glucose levels and inhibited by increased glucose level, increase plasma glucose by decreasing the entry of glucose into the cells and increasing glycolysis
ACTH
produced by anterior pituitary, released on stimulation by decreased cortisol, stimulate the anterior pituitary to release cortisol, increase plasma glucose by converting liver glycogen to glucose and promoting gluconeogenesis
Thyroxine
produced by thyroid gland, released on stimulation by TSH, increase plasma glucose by increasing glycogenolysis, gluconeogenesis and intestinal absorption of glucose
Somatostatin
increase plasma glucose by decreasing entry of glucose into cells and increasing glycolysis, secreted by D cells of Langerhans, increase plasma glucose by inhibiting insulin, glucagon, growth hormone and other endocrine hormones
Insulin
primary hormone responsible for entry of glucose into the cell, synthesized by beta-cells of Langerhans, released when blood glucose levels are high, increase glycogenesis, lipogenesis and glycolysis, inhibit glycogenolysis
Glucagon
primary for increasing blood glucose level, synthesized by alpha-cells of Langerhans, released when glucose levels are low, increase plasma glucose by increasing glycogenolysis in liver and gluconeogenesis
Hyperglycemia
increase of plasma glucose caused by an imbalance of hormone
Diabetes Mellitus
hyperglycemia caused by defects in insulin secretion, insulin action, or both
Type 1 diabetes
occur in childhood or adolescence, loss of pancreatic islet cells and are dependent on insulin to sustain life and prevent ketosis. mainly result from cellular-mediated autoimmune destruction of the Beta-cells
Type 2 diabetes
hyperglycemia due to an individual’s resistance to insulin, relative deficiency, most cases of diabetes, adult onset, milder symptoms, greater tendency to develop hyperosmolar non-ketonic states
Gestational Diabetes
women who fail to augment insulin sufficiently during pregnancy, more common if family history of diabetes, usually return to normal postpartum, increased perinatal complications
Diagnosis of diabetes
depend on the type of hyperglycemia, easy for type 1 because hyperglycemia appears abruptly, is severe and has metabolic problems, difficult for type 2 because hyperglycemia is often not severe enough for patient to notice symptoms
Diagnosis criteria for type 1 and 2
random plasma glucose >= 200 mg/dL + symptoms, fasting plasma glucose >= 126 mg/dL, plasma glucose >= 200 mg/dL during oral glucose tolerance test
Impaired fasting glucose
fasting glucose levels >= 100 mg/dL but <126 mg/dL, have a 2-hour OGTT levels of >= 140 mg/dL but < 200 mg/dL
Retinopathy
cataract formation is the principal retinopathy of diabetes
Neuropathy
most common complication of diabetes, present with pain, numbness, tingling or burning sensation in extremities, dizziness and double vision
Nephropathy
proteinuria is first sign due to damage to glomerulus and capillaries, end-stage renal disease develops in 1/3 of patients with type 1
Glucose tolerance test
patient drinks 75g of glucose and a measurement is taken 2 hours later, if level is >= 200 mg/dL and is confirmed on another day, diabetes confirmed
Diagnostic criteria for gestational diabetes
1-hour post-load screening test of >= 140 mg/dL indicates the need to perform a 3-hour OGTT using 100 g glucose, diagnosed when 2 of the following 4 are met:
Fasting > 95 mg/dL
1 hour > 180 mg/dL
2 hours >= 155 mg/dL
3 hours >= 140 mg/dL
Methods of glucose measurement
serum, plasma or whole blood, with whole blood being 15% lower than in serum or plasma, must be refrigerated and separated from cells within 1 hour to prevent glucose loss, sodium fluoride ions or sodium iodoacetate used as anticoagulant
Glycated hemoglobin
formed when glucose reacts with the amino group of hemoglobin, is chemically stable. proportional to plasma glucose concentration, reflects average blood glucose level of previous 3 months, determined by glucose concentration and red blood cell life span
Affinity chromatography
measures total glycated hemoglobin, separation based on chemical structure using borate to bind glycated proteins, not affected by hemoglobin F, S, or C
HPLC
measures glycated hemoglobin A1c, separations based on change, may be affected by other hemoglobin variants
Microalbuminuira
albumin excretion >= 20 mg/day and <= 300 mg/day, increase in urinary albumin, early sign for nephropathy associated with diabetes and are useful in assisting diagnosis before proteinuria
Ketone bodies
products of beta-oxidation of fatty acid, include acetone, acetoacetic acid, and beta-hydroxybutyric acid, produced in carb deprivation or decreased carb usage, measured in serum or urine
Methods of ketone body measurement
urine reagent strip test to detect acetoacetic acid, automated instruments to detect beta-hydroxybutyric acid or acetoacetic acid based on pH
Finding of ketosis in diabetic patients
dehydration, electrolyte disturbances, acidosis, decreased bicarbonate and total carbon dioxide, increased serum osmolality, lowered sodium concentration, increased potassium, highly elevated glucose in non-ketotic hyperosmolar state, presence of autoantibody
Hypoglycemia
decreased plasma glucose levels, various causes, classified as postabsorptive and postprandial hypoglycemia
Postabsorptive hypoglycemia
fasting, failure to maintain a stable plasma glucose level due to loss of glycemic control during fast state, caused by metabolic conditions like beta-islet cell insulinomas, characterized by a nonsuppressible insulin-like activity in which the glucose level drops below normal fasting levels, lack spontaneous recovery of glucose level, featured by decreased plasma glucose levels during hypoglycemic episode
postprandial hypoglycemia
reactive, not as serious, result from excessive release in insulin that results in glucose levels dropping below normal fasting levels, characterized by spontaneous recovery of glucose level
Glycogen storage diseases
result from the deficiency of a specific enzyme that causes an alteration of glycogen metabolism, with a glucose-6-phosphate deficiency type 1 as the most common
