1. The Lipid Profile Lipid Profile is ordered in the following
types of patients, who have a family history of high cholesterol or
heart disease are obese are diabetic are hypertensive (high B.P) In
short, the patients who have high risk of developing
atherosclerotic diseases of blood vessels.
2. The Lipid Profile A complete cholesterol test, referred to
as a lipid panel or lipid profile, includes the calculation of four
types of fats (lipids): Total cholesterol Low-density lipoprotein
(LDL) cholesterol High-density lipoprotein (HDL) cholesterol
Triglycerides
3. Structure of Lipoproteins The plasma lipoproteins are
spherical macromolecular complexes of lipids and specific proteins
(apolipoproteins or apoproteins). composed of a neutral lipid core
(containing triacylglycerol and cholesteryl esters) surrounded by a
shell of amphipathic apolipoproteins, phospholipid, and
nonesterified (free) cholesterol They serve to transport lipids in
the aqueous environment of blood.
4. Size and density of lipoprotein particles: Chylomicrons are
the lipoprotein particles lowest in density and largest in size,
and contain the highest percentage of lipid and the lowest
percentage of protein. VLDLs and LDLs are successively denser,
having higher ratios of protein to lipid. HDL particles are the
densest having the most protein and least amount of lipids
5. LDL- Cholesterol LDL-Cholesterol is one of the major
culprits in the development of atherosclerotic heart disease The
function of LDL is to deliver cholesterol synthesized in the liver
to other cells, where it is used in membranes, or for the synthesis
of steroid hormones. Cells take up cholesterol by receptor-mediated
endocytosis. LDL binds to a specific LDL receptor and is
internalized in an endocytic vesicle. Receptors are recycled to the
cell surface, while hydrolysis in an endolysosome releases
cholesterol for use in the cell.
6. LDL- Cholesterol LDL cholesterol is the major cholesterol
found in the plaques formed in coronary and other atherosclerotic
vascular diseases. Levels of LDL- cholesterol below 1o0 mg./dl are
recommended for patients with a history of risk factor for heart
disease.
7. HDL- Cholesterol HDL-Cholesterol is called good cholesterol
because it is inversely related with the incidence of
atherosclerosis HDL is involved in reverse cholesterol transport.
Excess cholesterol from cells is brought back to the liver by HDL
in a process known as reverse cholesterol transport HDL travels in
the circulation where it gathers cholesterol and returns the
cholesterol to the liver via various pathways. The HDL-Cholesterol
level above 40 mg/dL in men and above 50 mg/dL in women is
desirable.
8. Background Uric acid is the final product of purine
catabolism in human beings. Approximately two thirds of total body
urate is produced endogenously, while the remaining one third is
accounted for by dietary purines.
9. Background Approximately 70% of the urate produced daily is
excreted by the kidneys, while the rest is eliminated by the
intestines. The blood levels of uric acid are a function of the
balance between the breakdown of purines and the rate of uric acid
excretion. Alterations in this balance may account for
hyperuricemia.
10. Mechanism of Hyperuricemia Therefore, there are two main
mechanisms of hyperuricemia: 1. Under excretion e.g chronic kidney
disease 2. Overproduction e.g rapid cell death such as in cancer
chemotherapy or a combination of these two mechanisms!!
11. Effects of Hyperuricemia Gouty Arthritis, Gouty Tophi Uric
acid calculi in urinary tract.
12. Gout Acute inflammatory monoarthritis caused by
precipitation of monosodium urate crystals in joints most commonly
in the great toe and less frequently in the tarsal joint, knee, and
other joints Results in intesnse pain, redness and swelling of the
affected joint. polarized light microscopy of the joint aspirate
show the presence of needle-shaped mono -sodium urate crystals
13. LABORATORY STUDIES Serum uric acid CBC count: Values may be
abnormal in patients with hemolytic anemia, hematologic
malignancies, or lead poisoning. Electrolytes, Urea, and serum
creatinine values: These are abnormal in patients with acidosis or
renal disease. Urinary uric acid excretion
14. KIDNEY DISORDERS and ASSESSMENT OF RENAL FUNCTION The
kidneys have many functions, most notably: excretion of waste such
as urea and creatinine maintenance of extracellular fluid (ECF)
volume and homeostasis Acid Base homeostasis hormone synthesis such
as erythropoeitin and vitamin D
15. THE NEPHRON The functional unit of the kidney is a nephron.
Each kidney contains approximately 1 to 1.5 million nephrons. A
nephron is in fact a long microscopic tubule, consisting of
different anatomic and functional units and supplied by a rich
blood supply.
16. Urine formation requiers : Urine Formation Glomerular
Filtration Due to differences in pressure water, small molecules
move from the glomerulus capillaries into the glomerular capsule
Tubular reabsorption many molecules are reabsorbed from the nephron
into the capillary (diffusion, facilitated diffusion, osmosis, and
active transport) i.e. Glucose is actively reabsorbed with
transport carriers. If the carriers are overwhelmed glucose appears
in the urine indicating diabetes Tubular secretion Substances are
actively removed from blood and added to tubular fluid (active
transport) ie. H+, creatinine, and some drugs are moved by active
transport from the blood into the distal convoluted tubule a) b)
c)
17. The structure of the nephron and the processes of urine
formation. (Source: Pearson Education/PH College) 03/05/2011
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18. The glomerular filtrate is an ultra filtrate of plasma;
that is, it has a similar composition to plasma except that it is
almost free of proteins. Proteins with molecular weights lower than
that of albumin (68 kDa) are filterable; negatively charged
molecules are less easily filtered than those bearing a positive
charge. . The volume of plasma fluid filtered from glomerular
capillaries into the Bowmans capsule per unit time is called
Glomerular Filtration Rate (GFR).
19. The normal glomerular filtration rate (GFR) is
approximately 120 mL/min, equivalent to a volume of about 170 L/24
h. However, urine production is only 1-2 L/24 h, depending on fluid
intake; the bulk of the filtrate is reabsorbed further along the
nephron
20. Laboratory Investigations in renal DIseases The most
routinely ordered tests in suspected kidney diseases are: Blood
urea Serum creatinine and Urinary albumin Increased blood urea and
creatinine levels in a patient of renal failure may be a sign of
decreased GFR However, urea and creatinine levels may be normal in
the initial stages of the kidney diseases due to the great ability
of the healthier parts of the kidney to compensate and maintain
adequate GFR.
21. Therefore, in many patients an estimate of GFR is made to
gauge the true extent of kidney damage. Creatinine clearance is
measured to estimate the GFR. Creatinine clearance is defined as
the volume of plasma which is cleared of creatinine per unit time.
Creatinine clearance is a good estimate of GFR because it is freely
filtered and only minutely secreted with no reabsorption.
22. Creatinine clearance is calculated from the formula: U
urinary creatinine concentration (mol/L) V urine flow rate (mL/min
or (L/24 h) P plasma creatinine concentration (mol/L)
23. Assessment of glomerular integrity Impairment of glomerular
integrity results in the filtration of large molecules that are
normally retained and is manifest as proteinuria. Proteinuria can,
however, occur for other reasons.
24. Classification of Proteinuria Albumin excretion below 30
mg/day ( less than 20 mcg/ min) : normoalbuminuria Persistent
albumin excretion between 30 and 300 mg/day (20 to 200 mcg/min) OR
albumin (g)/creatinine (mg) ratio, ACR>30 g/mg): high
albuminemia (formerly called microalbuminuria) Albumin excretion
> 300 mg/day (200 mcg/min; (ACR 300 g/mg)): overt proteinuria or
very high albuminuria (formerly called macroalbuminuria)
25. The liver INTRODUCTION The liver is of vital importance in
intermediary metabolism and in the detoxification and elimination
of toxic substances.
26. What does the liver do? Temporary nutrient storage
(glucose- glycogen) Remove toxins from blood Remove old/damaged
RBCs Secrete Bilirubin synthesized from breakdown of hemoglobin and
other heme containing proteins. Regulate nutrient or metabolite
levels in bloodkeep constant supply of sugars, fats, amino acids,
nucleotides (including cholesterol) Multi-function,
blood-processing factory
27. What does the liver do? Secrete bile via bile ducts and
gall bladder into small intestines. Secrete and synthesize Albumin
which maintains plasma fluid levels Synthesize proteins of the
blood clotting system. Removes ammonia from blood and synthesize
urea to be excreted in urine. Multi-function, blood-processing
factory
28. What targets the Liver? Toxins Alcohol Medications Tylenol
Mushrooms Tumors, most frequently secondary; Viral Hepatitis
A/B/C/D/E EBV/HSV/CMV Autoimmune
29. What targets the Liver? Metabolic Glycogen storage diseases
Wilsons Disease Ischemia Severe hypotension Vasoconstriction Sepsis
Deficiency diseases Alpha-1 antitrypsin deficiency
30. LIVER FUNCTION TESTS ALT : Alanine Transaminase AST :
Aspartate Transaminase ALP: Alkaline Phosphatase GGT: Gamma
Glutamyl Transferase Albumin reflects protein synthetic function
PT, aPTT and INR reflect clotting factor synthesis Ammonia: An
increase in serum ammonia reflects decreased synthesis of
urea.
31. Liver Function Tests and Markers of liver cell injury.
Damage to the liver may not obviously affect its activity since the
liver has considerable functional reserve, As a consequence, simple
tests of liver function (e.g. plasma bilirubin and albumin
concentrations) may not become abnormal until a significant damage
to liver has occurred. Therefore, they are insensitive indicators
of liver disease.
32. However, even a little damage to the hepatocytes will
result in increased tissue release of hepatic enzymes: acting as a
marker of liver cell injury. Therefore these enzyme assays are
sometimes, rightly called as Markers of Liver Cell Injury to
differentiate them from the TRUE Liver Function Tests
33. ALT and AST Enzymes, found in Hepatocytes Released when
liver cells damaged ALT is specific for liver injury AST (SGOT) is
also found in skeletal and cardiac muscle
34. Jaundice or Scleral Icterus Jaundice is a sign of many
hepatic diseases. Jaundice is defined as the yellowish
discoloration of skin and sclera of the eye. Elevated bilirubin
levels in blood (>2.5-3 mg/dL) cause jaundice. Bilirubin is the
end product of haem breakdown from hemoglobin and other haem
containing proteins Apart from hepatic diseases, jaundice may also
result from increased bilirubin formation such as hemolytic anemia
and biliary channel obstruction such as gall stones.
35. Thyroid Gland The thyroid gland produces three hormones:
Triiodothyronine or T3 Tetraiodothyronine, also called thyroxine,
or T4 Calcitonin Strictly speaking, only T3 and T4 are proper
thyroid hormones. They are produced in what are known as the
follicular epithelial cells of the thyroid, with iodine being one
of the main components of both hormones
36. Their most obvious overall effect on metabolism is to
stimulate the basal metabolic rate, oxygen consumption and heat
production, through actions that include stimulating Na+,K+-ATPases
involved in ion transport and increasing the availability of energy
substrates. Thyroid hormone can thus be considered as the Tuning
Switch of body metabolism. Thyroid Hormones Physiological
Functions
37. Thyroid Hormones Physiological Functions Body temperature
maintenance Increased heart rate and contractility. Lipolysis,
proteolysis, Glycolysis Mobilization of energy storage Brain
maturation in children Growth promotion in children.
38. Thyroxine synthesis and release are stimulated by the
pituitary trophic hormone, thyroid- stimulating hormone (TSH). The
secretion of TSH is controlled by negative feedback by the thyroid
hormones, which modulate the response of the pituitary to the
hypothalamic hormone, thyrotropin-releasing hormone (TRH).
REGULATION OF THYROID SECRETION
39. This feedback is mediated primarily by T3 produced by the
action of iodothyronine deiodinase on T4 in the thyrotroph cells of
the anterior pituitary. Glucocorticoids, dopamine and somatostatin
inhibit TSH secretion.
40. Thyroid function tests The tests used to investigate
thyroid function can be grouped into: Tests that establish whether
there is thyroid dysfunction Tests to know the cause of thyroid
dysfunction
41. Tests that establish whether there is thyroid dysfunction
TSH, T4 and T3 measurements Thyroid function tests
42. Tests to know the cause of thyroid dysfunction thyroid
auto-antibody and serum thyroglobulin measurements, thyroid enzyme
activities, biopsy of the thyroid, ultrasound and isotopic thyroid
scanning Thyroid function tests
43. TSH : - The single most sensitive, specific and reliable
test of thyroid status . - In primary hypothyroidism, [TSH] is
increased. - In primary hyperthyroidism, [TSH] is decrease or
undetectable
44. Total T4 and Total T3 : - More than 99% of T4 and T3
circulate in plasma bound to protein - Both [total T4] and [total
T3] change if [TBG] alters, e.g. in pregnancy Free T4 and Free T3
Free thyroid hormone concentrations are independent of changes in
the concentration of thyroid-hormone binding proteins more reliable
for diagnosis of thyroid dysfunction
45. Hyperthyroidism Clinical Features Palpitations Heat
intolerance Nervousness Insomnia Breathlessness Increased bowel
movements Light or absent menstrual periods Tachycardia Tremors
Weight loss Muscle weakness Warm moist skin Hair loss Staring gaze
In short everything speeds up and everything becomes
hyperactive
46. Hypothyroidism Clinical Features Dry skin Brittle and
lustreless hair Weight gain Tiredness Constipation Muscle aches
Bradycardia Cold intolarance Depression Memory Loss Menstrual
irregularities (menorrhagia) In short, everything slows down and
everything becomes dull.
47. The major causes and clinical features of hyperthyroidism.
Hyperthyroidism