Course Training Package_ biochemistrey-cardiac.docx

**Biochemistry** **[Theoretical Training Hours]** 20 hrs. **[Practical Training Hours:]** 20 hrs. \"Refer to Lab Training Manual\" **[Table of contents]** Course Description....................................................................................... 3 Course Goal................................................................................................\... 3 Course Objectives...................................................................................... 3 Course Outline..........................................................................................\... 4 Module 1, Introduction............................................................................... 8 Learning Objectives................................................................................. 8 Learning Activities & Related material...................................................... 9 **Organ Function**...........................................................................................10 Cardiac system........................................................................................10-21 Kidney function......................................................................................22-29 Liver function........................................................................................30-44 Pancreatic function.................................................................................45-60 Module 2 Lipid metabolism.................................................................................. 61-75 Module 3 Diabetes Mellitus.................................................................................. 76-82 Module 4 Thyroid gland........................................................................................83-100 Fertility hormones...............................................................................101-123 Adrenal gland.......................................................................................124-137 Pituitary gland................................................................................\....138-152 Parathyroids gland...........................................................................\...153-159 Module 5 Vitamins..............................................................................................160-182 Interference factor...............................................................................183-184 **[Course Description]** This course is intended as part of the training of medical laboratory graduates to enable them to work in medical labs. In this course the attendees will be introduced to medically important concepts related to Lab Biochemistry including practical & technical subjects, as well as the managerial issues in relation to this subject. In addition to exposing the participants to knowledge-building, skill-developing experiences. **[Course Goal]** At the end of the course, participants shall be able to comprehend & implement the practical issues in the Clinical Biochemistry; as applied in the medical laboratory whether basic or advanced, in addition to understanding the principles of interpreting the results in relation to the various clinical diagnoses and thereby assessing the validity or \"correctness\" of the result. Participants shall be able to perform all basic techniques & in certain cases the advanced procedures as well. **[Course Objectives]** The participants will be able to: 1\. Identify the real meaning of the test(s) requested 2\. Determine the pre-analytical requirements of the test (Phlebotomy & Data Entry) 3\. Apply the technical needs for performing the test, sample type & requirements 4\. Ability to apply proper pipetting and dividing the sample per section performed 5\. Analyze the sample whether applying manual test procedure or testing on instruments 6\. Ability to obtain the result in the post-analytical phase after passing all the steps required regarding approving Quality Control outcomes and accepting the result **[Course Outline]** +-----------------+-----------------+-----------------+-----------------+ | **[Module]{.und | **[Topics]{.und | **[Learning | **[Hrs.]{.under | | erline}** | erline}** | Outcomes]{.unde | line}** | | | | rline}** | | +=================+=================+=================+=================+ | [Module | - Introductio | - Significanc | 1.5 | | 1:] | n | e | | | | to concept | of | | | **Organ | of | individual | | | Function** | pathophysio | tests with | | | | logy | relation to | | | | | the organ | | | | - Organ | tested | | | | function in | explain the | | | | relation to | role of the | | | | specific | laboratory | | | | tests | in the | | | | related to | diagnosis | | | | the | and | | | | pathology | | | | | and disease | Organ function | | | | pathway. | in relation to | | | | | specific tests | | | | | related to the | | | | | pathology and | | | | - Cardiac | disease | | | | | pathway. | | | | - KFT | | | | | | - explain the | | | | - LFT | role of the | | | | | laboratory | | | | - Pancreatic | in the | | | | | diagnosis | | | | | and | | | | | management | | | | | of | | | | | myocardial | | | | | infarction, | | | | | liver | | | | | disease, | | | | | kidney | | | | | disease and | | | | | pancreatic | | | | | disease. | | +-----------------+-----------------+-----------------+-----------------+ | [Module | - Types of | - Understandi | | | 2:] | lipids | ng | | | | | lipid | | | **Lipid | - Why are | structure, | | | metabolism** | lipids | metabolism, | | | | important? | types of | | | [Module | | lipids, | | | 3] | - Relationshi | role of | | | | p | lipids in | | | **Diabetes | of all | body | | | Miletus** | lipid | | | | | parameters | - Relies the | | | | such as: | health | | | | | problem | | | | | associated | | | | | with high | | | | - Cholesterol | lipid. | | | | | | | | | - Triglycerid | - Definition | | | | es | of DM | | | | | | | | | - HDL, LDL | - Understandi | | | | | ng | | | | - Lipoprotein | of hormonal | | | | s | control of | | | | | body | | | | | glucose | | | | | | | | | - Hormonal | - Understandi | | | | control of | ng | | | | Diabetes | metabolism | | | | mellitus | of each | | | | | | | | | - Classificat | - Type of DM, | | | | ion | causes, and | | | | of Diabetes | related | | | | mellitus | interpretat | | | | | ion | | | | - Insulin | | | | | Dependent | - Significanc | | | | Diabetes | e | | | | Mellitus | of | | | | (IDDM) Type | individual | | | | 1 | laboratory | | | | | tests are | | | | - Non-Insulin | used in the | | | | Dependent | diagnosis | | | | Diabetes | and | | | | Mellitus | management | | | | (NIDDM) | of patients | | | | Type2 | with DM. | | | | | | | | | - Gestational | - Glucose | | | | Diabetes | test | | | | (GDM) | | | | | | - GTT | | | | | | | | | | - Post | | | | | prandial. | | | | | | | | | | - HBA1c | | | | | | | | | | - Insulin | | | | | | | | | | - Homa score | | | | | definition. | | +-----------------+-----------------+-----------------+-----------------+ | **Module 4:** | Significance of | - Significanc | | | | various | e | | | **Hormones** | hormones in | of | | | | relation to | individual | | | | certain organs | tests with | | | | such as: | relation to | | | | | the organ | | | | - Pituitary | tested. | | | | gland | | | | | Anterior | - Describe | | | | and | the | | | | Posterior | functions | | | | hormones | of various | | | | | hormones. | | | | - Fertility | | | | | hormones | | | | | Female and | | | | | male | | | | | | | | | | - Thyroid | | | | | gland | | | | | | | | | | - Adrenal | | | | | gland | | | | | | | | | | - Parathyroid | | | | | gland | | | +-----------------+-----------------+-----------------+-----------------+ | [Module | - Significanc | - Significanc | 5 | | 5] | e | e | | | | of basic | of | | | **Vitamins** | vitamins | individual | | | | that | tests with | | | | influence | relation to | | | | the general | the organ | | | | health of | tested. | | | | the | | | | | individual: | | | | | | | | | | | - Significanc | | | | | e | | | | - Vitamin B | of | | | | complex | individual | | | | | tests with | | | | - Vitamin D | relation to | | | | | the organ | | | | - Various | tested. | | | | vitamins | | | | | | - Describe | | | | | the | | | | | functions | | | | | of | | | | | vitamins. | | +-----------------+-----------------+-----------------+-----------------+ [ **Module: 1**] **[Organ Function]** - **[Introduction:]** In the clinical laboratory, the technician and technologist are responsible for producing (reporting) valid results from tests and procedures which aid in disease diagnosis and management. While performing the tests properly is a major part of that job, assessing the validity or \"correctness\" of the result is equally important. Part of assessing validity is knowing what a reasonable result for a particular patient is. This involves an understanding of disease processes and how they can affect physiology. The purpose of this module is to introduce you to the concept of pathophysiology. - **[Module Learning Objectives ]** To successfully complete the module competency, the learner will be able to comprehend. - Learners gained general overview about the role of cardiac biomarkers, and the characteristics of a good marker of cardiac disease, and the use of cardiac biomarkers today. Discuss CK-MB, myoglobin, and CK- , cTnI and cTnT measurement in diagnosis of an acute myocardial infarction. - Compare and contrast the specificity and sensitivity of the most used serum cardiac markers. - Identify BNP and NT-Pro BNP and their role as markers of congestive heart failure. - Interpret the measurement results of cardiac biomarker assays in the diagnosis of an acute myocardial infarction. **[Learning Activities ]** - Ask participants what they know about cardiac markers tests. - Present an introduction of heart disease and cardiac biomarkers. - Discuss the classification of cardiac markers. - Discuss features of an ideal cardiac marker. - Ask participants to discuss in groups tests related to myocardial damage, and beginning of time to occur abnormal activity, and the peak value in hours. Conclude the specificity and sensitivity of the most used serum cardiac markers. (10 min). - Ask groups to present their discussion points (5 minutes to each group) and write their points on flip chart. - Case study in-group discussion to make sure of right interpretation of measurement results of cardiac biomarker assays in the diagnosis of an acute myocardial infarction. - [**Connection Activities** ] - Ask Participants. - Are you satisfied with your profession? - How do you feel about being a Medical Technologist? - What are the challenges to our profession? ![I\'m Proud To Be Medical Laboratory Technologist Until I Win](media/image2.jpeg) - Ask participants about their knowledge of cardiac risk and related blood tests. - Ask participants about their knowledge of **ATHEROSCLEROSIS**, **MYOCARDIAL INFARCTION** - Ask groups to present their discussion points (3 minutes to each group) **[Learning methods/Activities]** - PowerPoint slides - Group discussion. - Flip Chart Demos - Illustrative images - Case study - Heart Disease and Cardiac Biomarkers**:** - Introduction - The heart is the centerpiece of the circulatory system. Blood vessels and the pumping action of the heart work together to regulate blood flow. - The heart consists of four chambers: two atria and two ventricles. The arteries have thick elastic walls (larger arteries) or muscular walls (smaller arteries) that work to accommodate the blood volume in their lumen. The veins have thinner walls and lack the elasticity or contractile capacity of the arteries. They have valves to prevent the back flow of blood as it returns to the heart. - Heart disease is a consequence of impaired cardiac pumping ability and fluid retention**[.]** - Diseases of the heart may affect the pericardium, the myocardium or the endocardium -- in particular the endocardium that covers the valves. The heart is a pump, and its failure leads to circulatory disturbances and death. - Cardiac enzymes are molecules released into the circulation as a consequence of cardiac injury. - They are used in the diagnosis of myocardial infarction, but elevations are not synonymous with an ischemic mechanism of injury and results should be interpreted in the context of clinical and ECG findings. - Cardiac biomarkers are important in heart disease where there. is damage to the myocardium and myocytes. - Interrupted or blocked blood flow and decreased oxygen cause injury to the myocytes and eventually cell death. - As the myocytes become necrotic, their membranes are disrupted. and intracellular biomolecules diffuse into the cardiac microvasculature. - These compounds, which are biomarkers that can be measured, then. enter the peripheral circulation. - Cardiac biomarkers are relied upon for detection and monitoring. of two categories of cardiovascular disease: - Acute ischemic disease (acute myocardial infarction (AMI). - Heart failure. - Markers of myocardial damage. - Markers of coronary risk. - Markers of congestive heart failure [ **Optimal Cardiac Biomarkers** ] An ideal marker for cardiac disease would have all these characteristics: - Specific to myocardial tissue. - Low concentrations in normal (healthy) peripheral blood. - Rapidly released after myocardial injury. - Remains in circulation for a sufficient length of time for detection. - Plasma concentration of the marker directly related to the extent of injury. Markers of myocardial damage 1. AST (SGOT) 2. LDH (Lactate Dehydrogenase) 3. CK (Creatine kinase) 4. CK-MB 5\. Myoglobin 6\. Troponin: Troponin I (cTnI), Troponin T (cTnT -. Aspartate Aminotransferase ( AST ) GOT - The first cardiac markers to be used extensively in clinical practice. - AST is found predominantly in the cytoplasm(c-AST), and mitochondria(m-AST) - AST is widely distributed in equal amounts in the heart, skeletal. muscle, liver and kidney. - Normally present in Plasma, the serum concentration are raised when any of the above tissues are damaged. - Clinical significance: 1. Acute hepatocellular damage 2. Myocardial infarction 3. Congestive heart failure. 4. Biliary tract obstruction 5. Cholicyctisis - AST is non-specific as cardiac markers. - LDH (lactate dehydrogenase) - Lactate dehydrogenase (LDH) is an important enzyme of the anaerobic metabolic pathway. - LDH is an oxidoreductase which catalyses conversion. of lactate to pyruvate, an enzyme that is part of the glycolytic pathway. - LDH is a tetramer of two active subunits, H (heart) &M (muscle). Combinations of subunits produce five isoenzymes (LDH-1 through LDH-5) - LDH is non-specific and routine isozyme measurement is usually unavailable in clinical laboratories, ( If LDH-1 is found to be greater than LDH-2, it indicates myocardial infarction, ) - Usually LDH isoenzyme levels increase 24--72 hours following myocardial infarction and reach a peak concentration in 3--4 days. - Compared with AST, LDH was found to be a more sensitive marker. of MI that remains elevated for significantly longer post-MI, up to 2 weeks. A table with text on it Description automatically generated - CK (CREATINE KINASE) - CK transfers high energy phosphate between creatine. and ADP, mainly in muscle cells, but it is found in all types of muscle and in brain. - In a typical patient with acute MI, serum CK levels will exceed the normal range within 6 to 8 hours, to reach. a peak of two to ten-fold normal by 24 hours, and then decline to the normal range after 3 to 4 days. Clinical Significance: CPK (Creatine phosphokinase) activity is increase in - Brain (CK-BB) Cerebro-vascular stroke - heart muscle (CK-MB) - Myocardial infarction - Acute coroary syndrome - skeletal muscle. (CK-MM = 85%) - Crush injury (trauma) - Myopathy - Polymyositis - CK-MB [ ] - The cytoplasmic isoenzymes are dimers composed of combinations of M and B subunits (where M is for muscle and B is for brain). - Elevations CK-MB in serum could be detected at 4 to 6 hours. After the onset of MI symptoms, CK-MB levels quickly drop. to baseline levels by 2 to 4 days post-MI. - CK-MB is present only in cardiac tissue. - So...Specific for diagnosis of cardiac disease. - Myoglobin - Myoglobin is a heme-containing protein that binds oxygen. within cardiac and skeletal muscles. - Myoglobin is present in all muscles, not just cardiac muscles. - It is released earlier after muscle injury than other cardiac. enzymes and returns to normal faster than either of these markers. - It rises within 2‐4 hours after chest pain. peaks in 6‐12 hours and is usually normal within 24‐36 hours. - Unfortunately, [myoglobin](https://www.sciencedirect.com/topics/medicine-and-dentistry/myoglobin) is not specific for the death of cardiac myocytes, and levels can be elevated in [renal disease](https://www.sciencedirect.com/topics/medicine-and-dentistry/nephropathy) as well as damage to [skeletal muscle](https://www.sciencedirect.com/topics/medicine-and-dentistry/skeletal-muscle) - CK-MB and myoglobin tend to provide the earliest detection of a possible MI (less than 6 h). This is important because thrombolytic drugs may be administered within the ideal time frame. It is important to note that myoglobin testing is not specific for heart muscle. - [Cardiac Troponins] - Troponin (Tn) is a component of the heart muscle and its release is indicative of early events in heart [tissue degeneration](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/tissue-degeneration), necrosis, and myocyte damage - The troponin class of proteins are all contractile proteins. - Its major regulatory function is to bind calcium and regulate muscle contraction. - They work with calcium ions and another protein called tropomyosin. - There are three types of troponin proteins: - Troponin C ‐‐ Calcium‐binding component. - Troponin I ‐‐ inhibits (contraction) actomyosin ATPase. - Troponin T \--Tropomyosin binding component (facilitates contraction) - TnC is expressed in both cardiac and [skeletal muscle](https://www.sciencedirect.com/topics/medicine-and-dentistry/skeletal-muscle), while TnT and TnI are expressed almost exclusively in the heart and commonly referred to as [cardiac troponins](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/cardiac-troponin) (cTn). - Cardiac troponins are detectable in plasma at 4 to 12 hours. after myocardial injury. - Peaking at 12 to 24 hours and remaining elevated for more than 1 week: 8 to 21 days for TnT and 7 to 14 days for TnI. - It is measured as an early indicator of an AMI. - Cardiac troponins thus offer the widest window for detection. post-MI, and with the highest sensitivity and specificity. [ ] ![](media/image4.png) +-------------+-------------+-------------+-------------+-------------+ | **CARDIAC | | | | | | MARKERS AND | | | | | | EXPECTED | | | | | | RESULTS IN | | | | | | MI** | | | | | +-------------+-------------+-------------+-------------+-------------+ | **Marker** | **First | **Peaks** | **Duration* | **Relative | | | Detected** | | * | Increase | | | | **(h)** | | (XULN)** | | | **(h)** | | **(d)** | | +-------------+-------------+-------------+-------------+-------------+ | Myoglobin | 2-5 | 8-10 | 1 | 6 | +-------------+-------------+-------------+-------------+-------------+ | Troponin | 4-6 | 24-48 | 7 | 50 | | (T, I) | | | | | +-------------+-------------+-------------+-------------+-------------+ | CK | 6-8 | 24-36 | 3 | 10 | +-------------+-------------+-------------+-------------+-------------+ | CK-MB | 3-4 | 24 | 2-4 | 10 | +-------------+-------------+-------------+-------------+-------------+ | AST | 8-10 | 24 | 3-4 | 5 | +-------------+-------------+-------------+-------------+-------------+ | LD | 10-12 | 48-72 | 5-10 | 4 | +-------------+-------------+-------------+-------------+-------------+ | | | | | | +-------------+-------------+-------------+-------------+-------------+ - Case study - Select the correct statements regarding troponins. More than one answer is correct. Please select all correct answers: 1. cTnI and cTnT can remain elevated for several days following an AM.- 2. Only cTnT remains elevated for several days following an AMI. 3. Troponin C, troponin T, and troponin I are measured in risk stratification in patients with ACS. 4. If multiple testing is performed on a patient with an AMI, a second peak may be seen if cTnT is the biomarker that is used. - cTnI is easier to measure than cTnT. - Which of the following cardiac biomarkers can be used as a stand‐alone marker, and is therefore the preferred biomarker to indicate the presence of an AMI? Please select the single best answer 1. Cardiac troponin - 2. CK‐MB 3. Myoglobin - A 62‐year‐old male has been brought by ambulance to the emergency department. The patient is a smoker with a history of uncontrolled hypertension. While doing some outside painting at home, he became light‐headed and complained of sharp pains in his chest. - In the emergency department, an ECG and cardiac troponin I ﴾cTnI﴿ serial testing are ordered. There is an abnormal ST elevation seen with ECG. - Baseline cTnI = 0.03 ng/Ml - 8 Hours cTnI = 0.5 ng/mL Can this patient be diagnosed with an AMI according to the latest guidelines? Please select the single best answer 1. No, there would need to be a cTnI drawn at 12‐24 hours before conclusion are drawn. 2. Yes, the abnormal ECG is sufficient for an AMI diagnosis. 3. No, there needs to be an elevated CK‐MB also for an AMI diagnosis. Yes, elevated cardiac biomarkers and abnormal ECG indicate an AMI. - - While driving home after work, a 45‐year‐old male construction worker is involved in a collision with another car. Upon arrival in the emergency department, the patient complains of chest pain along with severe pain from accident injuries. X‐rays and laboratory assays including cardiac biomarkers are ordered. - Do the cardiac marker results indicate that an AMI is causing his chest pain? Please select the single best answer. - - **Markers of coronary risk** - Measurement of substances that are damaging to the coronary arteries, - or at least have proven association with coronary heart disease (CHD). - Are used to assess risk and select appropriate preventive measures. - The most important laboratory risk factors are lipids, homocysteine & C-reactive protein. - **High Sensitivity C‐Reactive Protein (hs‐CRP)** - Because atherosclerosis and CHD derive from an inflammatory etiology. CRP has long been targeted as a biomarker for CHD. - Clinical uses: - Screening for cardiovascular risk in otherwise "healthy" individual. - Predictive value of CRP levels for disease severity in pre-existing coronary artery disease. - Because atherosclerosis and CHD derive from an inflammatory etiology. CRP has long been targeted as a biomarker for CHD. - Clinical uses: - Screening for cardiovasular risk in otherwise "healthy" individual. - Predictive value of CRP levels for disease severity in pre-existing coronary artery disease. - **Homocysteine** - Homocysteine is a sulfur-containing amino acid formed in plasma from the metabolic demethylation of methionine, which is derived from dietary protein. - A deficiency of any of the vitamin cofactors involved in metabolism of Hcy: folate, B12, or pyridoxine (B6) cause elevation of homocysteine. - An elevation level of homocysteine in the blood cause narrawing & hardening of arteries (atherosclerosis). Which leads to diminished blood flow and increase tendency to excessive blood clotting. - The resultant lack of blood supply to heart muscle may cause heart attack and lack of blood supply to brain causes stroke. - **Markers of congestive heart failure** - The heart can act as an endocrine organ. - Cardiac neurohormone specifically secreted from the ventricles in response to increased wall stress (pressure or volume). - Released as prohormone which is then cleaved into active hormone BNP and NT-proBNP. - BNP is a diuretic. Once released, stimulates natriuresis and water loss. BNP causes loss of sodium and water through the kidneys to relieve the ventricular wall stretch. - BNP Versus NT‐ProBNP - BNP, an active protein hormone, has a short biological. - half‐life of around 20 minutes. - The inactive fragment NT‐ProBNP, has half‐life of 1‐2 hours. - NT‐ProBNP is thought to be primarily cleared by kidneys and - therefore, falsely elevated in severe renal disease. - Both increased in CHF and correlate to the severity of condition. - Differentiate patients whose pulmonary disease presents with - symptoms like CHF. - Case study - 1)What is the function of the hormone, BNP? Please select the single best answer - Stimulate the reabsorption of sodium and water. - Stimulate the excretion of sodium and water. - - Activate NT‐ProBNP. - Increase the force of ventricular contractions. - A 79‐year‐old diabetic and retired homemaker lives alone since the death of her husband 5 years ago. At age 75, she was diagnosed with an AMI and had another AMI last year. In the past 6 weeks, she has been weak and often lacks energy. For the past 2 days, her symptoms have worsened, and she is short of breath with any exertion. Her daughter brings her to see the cardiologist who orders a BNP to evaluate her cardiac disease. BNP 520 pg/mL (Reference value = \ - Treatment of myocardial infarction usually includes administration of an anticoagulant to reduce the chance of clots forming on whatever is occluding the coronary vessels. - The role of the laboratory with anticoagulant treatment is to evaluate the ability of the patient\'s blood to form a clot. - This clotting ability must be reduced enough to prevent thrombosis or embolism formation, and yet protect the patient from spontaneous hemorrhage. - When a blockage has occurred causing myocardial infarction thrombolytic agents are given to dissolve the clot. (streptokinase, urokinase and tissue plasminogen activator (TPA).) - The two main coagulation tests are used to monitor anticoagulant therapy are: Activated Partial Thromboplastin Time (APTT) - Heparin therapy Prothrombin Time (PT) - Coumadin therapy **Kidney function** - Objective - The participants will be able to: - Describe The anatomy of kidney? - List the Maine analyte that estimates kidney function. - Define eGFR role in glomerular function. - Discuss the endocrine role for kidneys. - Understanding the main kidney disorder - **What are the kidneys?** - The kidneys are vital organs, two bean-shaped responsible for clearing waste products, salts, and water from the body. and are part of the urine system. - **[Anatomy:]** - Kidneys are highly complex organs with many parts. The main parts of kidney anatomy include: - **Renal capsule**: The renal capsule consists of three layers of connective tissue or fat that cover the kidneys. It protects kidneys from injury. - **Renal artery:** The renal artery is a large blood vessel that controls blood flow into your kidneys. - **Renal cortex:** The outer layer of your kidney, where the nephrons (blood-filtering units) - **Renal medulla:** The renal medulla is the inner part of your kidney. It contains most of the nephrons. - **Renal papilla:** These pyramid-shaped structures transfer urine to the ureters. - **Renal pelvis:** This funnel-shaped structure collects urine and passes it down two ureters. - **Renal vein: This** vein is the main blood vessel that carries filtered blood out of kidneys and back to heart. - ![](media/image7.png) - **[Renal physiology]:** - Each kidney contains more than a million filtering units called nephrons. Each nephron consists of: - **[Glomeruli]:** are groups of tiny blood vessels that perform the first stage of filtering your blood. They then pass filtered substances to the renal tubules. The name for this process is **glomerular filtration.** - **[Renal tubules:]** These tiny tubes **reabsorb** and return water, nutrients, and minerals what body needs (including sodium and potassium). The \`tubules remove waste, including excess acid and fluids through diffusion. - **[Function:]** - The main functions of kidneys are: - **Excretion** of wastes: kidneys excrete Nonprotein nitrogen compounds, urea, creatinine, and uric acid into the urine, which are products of nucleic acids, amino acids, and proteins metabolism. - **Reabsorption** of vital nutrients, which includes glucose (at normal plasma level), amino acids, water, sodium, chloride, potassium, magnesium, calcium, bicarbonate, and phosphate. - **Acid-Base homeostasis**: which is maintenance of balance between chemical acids and bases, also called body PH. Retention of biologically active substances (glucose, amino acids, minerals, vitamins) by differential reabsorption throughout tubules. - **Maintenance of Electrolyte**-Water balance: which is called plasma osmolarity. - **Hormone secretion**: kidneys secrete Erythropoietin (regulates the production of red blood cells in bone marrow), Renin (controls blood pressure) and Calcitriol (active form of vitamin D). - **[KIDNEY FUNCTION TESTs]** - Kidney function tests are a group of blood tests that provide information on how well [ ] kidney works. - The components of the Kidney function test can be broadly divided into two categories: - Tests that measure glomerular function (eGFR,crs,urea..) - Tests that measure tubular (reabsorption, acid base) function,(ELE,PHS..) - Urine examination: Important for assessing both glomerular and tubular function. - **[The tests measure levels of various substances in blood, including:]** - **electrolytes**: sodium, potassium, chloride, bicarbonate - **minerals**: phosphorus, calcium - **protein**: albumin - **waste products**: urea, creatinine, uric acid - **Urine** **eGFR:** (estimated glomerular filtration rate**):** This is a measure of the amount of blood that's filtered by your kidneys each minute. This is a good indicator of how well your kidneys are working. - [Why are kidney function tests?] -------------------------------------------- - a screening test if you're at risk of kidney disease. ----------------------------------------------------- - have kidney disease, to monitor and manage your treatment. - have [high blood pressure](https://www.healthdirect.gov.au/high-blood-pressure-hypertension) or [heart disease](https://www.healthdirect.gov.au/coronary-heart-disease-and-atherosclerosis) - are living with [diabetes](https://www.healthdirect.gov.au/diabetes) - are taking medicine that might affect your kidneys. - [Creatinine test ] - Creatinine is a waste product produced in muscles from the breakdown of a compound called creatine. - Creatine is part of the cycle that produces energy needed to contract muscles. - Almost all creatinine is excreted by the kidneys, so blood levels are a good measure of how well kidneys are working. - The quantity produced depends on the sex, size or age of the person and their muscle mass. For this reason, creatinine concentrations will be slightly higher in men than in women and children. - **[Increased creatinine levels in the blood suggest diseases that affect kidney function. These can include:]** - damage to or swelling of blood vessels in the kidneys (glomerulonephritis) caused by, for example, infection. - death of cells in the kidneys' small tubes (acute tubular necrosis). - reduced blood flow to the kidney. - Creatinine blood levels can also increase temporarily because of muscle injury and are generally slightly lower during pregnancy. - Low levels of creatinine are not common and are not usually a cause for concern. Creatinine levels are related to the amount of muscle the person has. - **[Blood urea test ]** - Urea is the final breakdown product of the [amino acids](https://labtestsonline.org.uk/glossary/amino-acid) found in [proteins](https://labtestsonline.org.uk/glossary/protein). - Nitrogen in the form of ammonia is produced in the liver when protein is broken down. - The nitrogen combines with other chemicals in the liver to form the waste product urea. - The urea is released into the bloodstream and carried to the kidneys where it is filtered out of the blood and excreted in the urine. - Healthy kidneys remove more than 90% of the urea the body produces, so blood levels can show how well your kidneys are working. - **[Urea is often requested with creatinine:]** - if kidney problems are suspected, - to monitor treatment of [kidney disease](https://labtestsonline.org.uk/conditions/kidney-disease), or to monitor kidney function while someone is on certain drugs. - **Uric acid test** - Uric acid is produced by the breakdown of purines, which are nitrogen-containing compounds found in the body in substances such as nucleic acids ([DNA](https://labtestsonline.org.uk/glossary/dna), [RNA](https://labtestsonline.org.uk/glossary/rna)). - They enter the circulation from digestion of certain foods, drinks or from normal breakdown and turnover of cells in the body. - Most uric acid is removed by the kidneys and disposed of in the urine; the remainder is excreted\... - What is **hyperuricemia?** - A higher level of uric acid than normal in the blood is called hyperuricemia and can be caused by the over-production of uric acid in the body or the inability of the kidneys to clear out enough uric acid. - Increased concentrations of uric acid can cause crystals to form in the joints, which leads to the joint inflammation and pain characteristic of [gout](https://labtestsonline.org.uk/understanding/conditions/gout). - Uric acid levels rise in chronic kidney disease (CKD) and may lead to tubular injury, endothelial dysfunction, oxidative stress, and intra-renal inflammation. [ELECTROLYTES TETS] ------------------------------- - Electrolytes are minerals that carry a charge and exist in body fluids. ----------------------------------------------------------------------- - Sodium and other electrolytes such as [potassium](https://www.testing.com/tests/potassium/), [chloride](https://www.testing.com/tests/chloride/), and [bicarbonate (or total CO2)](https://www.testing.com/tests/bicarbonate-total-co2/) help cells function normally and regulate the body's fluid --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- - [Sodium level] -------------------------- - While sodium is present in all body fluids, it is found in the highest concentration in the blood and the fluid outside of the body's cells. This extracellular sodium, as well as all body water, is regulated by the kidneys. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- - When the level of sodium in the blood changes, the water content in the body also changes. These shifts can be associated with too little fluid (dehydration) or too much fluid (edema), often resulting in leg swelling. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- - A low concentration of blood sodium is called **hyponatremia**, and is usually due to too much sodium loss, too much water intake or retention, or fluid accumulation in the body ([oedema](https://labtestsonline.org.uk/glossary/edema)). - Low sodium level can be associated with: Weakness, Confusion, and lethargy. - A high blood sodium concentration is referred to as **hypernatremia,** and is almost always due to excessive loss of water ([dehydration](https://labtestsonline.org.uk/glossary/dehydration)) without enough water intake. - symptoms of high sodium, such as: Thirst, Dry mucous membranes, less frequent urination, Muscle twitching. **[Potassium level]** - Potassium is present in all body fluids, but most potassium is within cells. Only a very small amount of potassium is contained within the [serum](https://labtestsonline.org.uk/glossary/serum) or [plasma](https://labtestsonline.org.uk/glossary/plasma) component of the blood. - Blood potassium are measured as part of routine health screening and in those who take [diuretics](https://labtestsonline.org.uk/glossary/diuretic) or heart medications, and in the investigation of [high blood pressure ](https://labtestsonline.org.uk/conditions/hypertension-high-blood-pressure)and [kidney disease](https://labtestsonline.org.uk/conditions/kidney-disease). - A raised blood potassium concentration is called **hyperkalemia**. [Kidney disease](https://labtestsonline.org.uk/conditions/kidney-disease) is a common cause of hyperkalaemia. In this condition the body is less able to excrete potassium in the urine and so the levels within the blood rise**.** - A low blood potassium concentration is called **hypokalemia.** Hypokalaemia can occur due to excessive loss of potassium, for example due to severe diarrhea and vomiting. - [Potassium has important functions for:] - It allows the nerves to respond to stimulation and [muscles](https://www.healthdirect.gov.au/bones-muscles-and-joints) to contract (tighten), including those in the heart. - It reduces the effect of sodium on [blood pressure](https://www.healthdirect.gov.au/what-is-a-healthy-blood-pressure)(increasing potassium intake decrease blood pressure). - It helps move nutrients into cells, and waste products out of cells. **[Chloride level]** - Chloride is an [electrolyte](https://labtestsonline.org.uk/tests/electrolytes-and-anion-gap). When combined with sodium it is mostly found in nature as "salt." - Chloride is important in maintaining the normal [acid-base balance](https://labtestsonline.org.uk/glossary/acid-base) of the body and, along with sodium, in keeping normal levels of water in the body. - Chloride generally increases or decreases in direct relationship to sodium, but may change without any change in sodium when there are problems with too much [acid](https://labtestsonline.org.uk/glossary/acid) or [base](https://labtestsonline.org.uk/glossary/base) in your body. - Most of the chloride is absorbed by the gastrointestinal tract, and the excess is excreted in urine. The normal blood concentration remains steady, with a slight drop after meals (because the stomach produces hydrochloric acid after eating, using chloride from blood). - Increased levels of chloride (called hyperchloraemia) usually indicate dehydration. - Hyperchloraemia also occurs when too much alkaline fluid is lost from the body (producing metabolic acidosis), \' - Decreased levels of chloride (called hypochloraemia) occur with any disorder that causes low blood sodium. - Hypochloraemia also occurs with prolonged vomiting or gastric suction, chronic diarrhoea, emphysema, or other chronic lung disease (causing respiratory acidosis), and with loss of acid from the body (called metabolic alkalosis). **[Bicarbonate]** - hydrogen ion concentration (\[H+\], described by pH) must be kept within tight limits to prevent major health problems. - The ratio between blood bicarbonate (HCO~3-~) concentration and partial pressure of carbon dioxide (PCO~2~) determines blood pH. - Acid-base balance is linked to fluid and electrolyte (charged ion) balance so bicarbonate may be measured wit an [electrolyte profile](https://labtestsonline.org.uk/tests/electrolytes-and-anion-gap) to give the most information. - Metabolic acidosis occurs when low blood pH (acidaemia) is caused by a low bicarbonate concentration. - Causes of raised anion gap metabolic acidosis include Diabetes (diabetic ketoacidosis), Kidney disease, Drug overdose (e.g. paracetamol and salicylate). - Metabolic alkalosis occurs when a high blood pH (alkalemia) is caused by a high bicarbonate concentration (Severe vomiting, Low potassium, Blood transfusions). - Calcium is one of the most important minerals in the body, required for proper functioning of muscles, nerves, heart, as well as essential in blood clotting and bone formation. - About 99% of calcium is found in the bones, while most of the rest circulates in the blood. - In the blood, roughly half of the calcium is 'ionized' (or free) and is active; the remaining half, is bound to [albumin](https://labtestsonline.org.uk/tests/albumin). - The amount of calcium in the blood is controlled by the combined actions of [parathyroid hormone](https://labtestsonline.org.uk/tests/pth) (PTH) and [1, 25-dihydroxyvitamin D](https://labtestsonline.org.uk/tests/vitamin-d) (Vitamin D). - A high calcium level is called hypercalcemia**,** the main causes are ***Hyperparathyroidism** and in **Cancer*****:** (Cancer can cause hypercalcemia when it spreads to the bones**).** - Other causes of hypercalcaemia include Acute kidney injury, excess [Vitamin D](https://labtestsonline.org.uk/tests/vitamin-d) intake. - **[Phosphorous(phosphate)]** - The serum phosphate test measures the amount of inorganic phosphate blood, Phosphate works very closely with calcium, and they are frequently measured together. - In the body, phosphorus is combined with oxygen to form a variety of phosphates (PO~4~). - Phosphates are vital for energy production, muscle and nerve function, bone growth, and forms the building blocks for cell membranes and DNA. They also play an important role as a buffer, helping to maintain the body's [acid-base balance](https://labtestsonline.org.uk/glossary/acid-base). - About 85% of the phosphates are combined with calcium to help form bones and teeth and about 15% is found in soft tissues. The rest is found within cells throughout the body, where it is mainly used to store energy; and about 1% of your total body phosphate is found within the plasma. - phosphate testing often is performed as a follow-up to an abnormal [calcium](https://labtestsonline.org.uk/tests/calcium-test) level and/or related symptoms, such as fatigue, muscle weakness, cramps or bone problems. - Low levels of phosphate (hypophosphataemia) may also be due to or associated with: - Hypercalcemia, Diabetic ketoacidosis, Rickets, Hypokalemia, hypothyroidism. - Higher than normal levels of phosphate (hyperphosphataemia) may be due to or associated with: Kidney failure, Hypocalcemia, Vitamin D overuse. - **[eGFR (]Estimated Glomerular Filtration Rate**) - In the UK, the National Institute for Health, and Care Excellence (NICE) guidance states: "Whenever a request for serum creatinine measurement is made, clinical laboratories should report an estimate of GFR (eGFR)". - eGFR or Calculated Creatinine Clearance is a simple test to detect early changes in kidney function. - A normal result means that kidney disease is less likely while a low value suggests that some kidney dysfunction is present. - Estimated glomerular filtration rate (eGFR) measures how much substance in blood that kidney can filters every minute per milliliters through glomerulus based on body size. - **[Differences between eGFR and mGFR]** - eGFR A **calculation** used to estimate how well kidneys are filtering certain agents **produced by** body, such as: creatinine and cystatin C (a protein that slows down the breakdown of other protein cells) - mGFR A **measurement** of how well kidneys are filtering certain agents **not produced** by body, such as: inulin (a kind of fiber that is found in some plant foods). - To determine eGFR, uses the National Kidney Foundation calculating system. You need to: Creatinine level, age,sex, race. - **[Albumin]** - Albumin is a [protein](https://labtestsonline.org.uk/tests/protein) that is present in the blood. When the kidneys are working properly, only tiny amounts of albumin pass from the bloodstream into the urine. - In kidney failure large amounts of protein leak into the urine. small changes in the kidney often because of having [diabetes](https://labtestsonline.org.uk/conditions/diabetes) allow abnormal amounts of albumin to leak through. - Too little albumin is present to be detected by the usual simple urine test strip. This is termed microalbuminuria because of the low (but significant) concentration of albumin in the urine, not because it is a smaller type of protein. Microalbuminuria is usually simply called albuminuria. - **What are ACR(***Albuminuria)***?** - Albuminuria is increased excretion of urinary albumin and a marker of kidney damage. - A routine dipstick is not sensitive enough to detect small amounts of urine protein. Therefore, it is recommended that screening in adults with CKD or at risk for CKD be done by testing for albuminuria. - Albumin-to-creatinine ratio (**ACR**) is the first method of preference to detect elevated protein. The recommended method to evaluate albuminuria is to measure urinary ACR in a spot urine sample. - ACR is calculated by dividing albumin concentration in milligrams by creatinine concentration in grams. - **[Endocrine function]** - The kidney has multiple endocrine roles; it secretes various hormones and humoral factors: the hormones of the renin- angiotensin system (RAS), erythropoietin (EPO), and 1,25 dihydroxy vitamin D3. - [Renin:] - Is a proteolytic enzyme produced by the juxta glomerular cells of the renal medulla when extracellular fluid volume or blood pressure decreases. - Measurement: collect in EDTA plasma, fasting, specimen between 8 -10 AM, Determine the position of patient (supine or upright) Draw blood into ice- cooled tube. - [Erythropoietin:] - Erythropoietin is a hormone (single-chain polypeptide) that plays an important role in making red blood cells. - Its production is regulated by blood oxygen levels. Hypoxia produces increased serum concentrations within 2 hours. - Erythropoietin acts on the erythroid progenitor cells in the bone marrow, increasing the number of red blood cells (RBCs). - In chronic renal insufficiency, erythropoietin production is reduced. - RENAL DISEASE - Several facts important for understanding renal pathology are as follows: - The formation of urine depends on sufficient blood flow and adequate hydration of the body. - Obstruction of urinary passages will result in urine retention. - The urinary tract is extremely sensitive to bacterial infections. - The glomeruli are affected by many diseases that involve the vasculature (i.e. arteriosclerosis, hypertension, diabetes mellitus). - Renal tubules are composed of highly specialized cells that are very sensitive to loss of oxygen and nutrients, as well as to the adverse effects of toxins (i.e. drugs, poisons, heavy metals, endogenous wastes); - The urinary tract consists of many mitotic cells that may undergo malignant transformation. - VASCULAR DISEASE - Circulatory disturbances and vascular diseases affect the kidneys in many forms and may be acute or chronic. Principle causes of vascular disease include arteriosclerosis, thrombosis, embolism and vasculitis. In general, clinical changes may include loss of concentrating power, mild proteinuria, occasional urinalysis abnormalities and a normal or slightly reduced GFR. - GLOMERULAR DISEASE - Disorders or diseases that directly damage the renal glomeruli may, at least initially, exhibit normal tubular function but as the disease progresses the renal tubules may become involved. - Glomerular disease can be the result of immunologic diseases (i.e. poststreptococcal infections, membranous nephropathy), metabolic disorders (i.e. diabetes mellitus), circulatory disturbances (i.e. hypertension, atherosclerosis) or other conditions such as systemic lupus erythematosus. One of the first signs of glomerular disease is microalbuminuria. - GLOMERULONEPHRITIS - The primary injury in glomerulonephritis is to the glomeruli and is most often due to the deposition of immune complexes within the basement membrane. - Glomerular injury results not from immune complexes but from the chemical mediators and toxic substances that they produce. - Local inflammatory response increases the glomerular tissue damage further allowing larger molecules such as protein and red blood cells to escape into the filtrate. - Loss of protein, mostly albumin, causes hypoalbuminemia which in turn, results in edema. This is because a decrease in the oncotic (colloidal) pressure of plasma allows fluid to escape into interstitial spaces. Reduced blood flow through the arterioles leading to the inflamed glomeruli elicits the release of renin resulting in hypertension. - TUBULAR DISEASE - Diseases affecting the tubules as well as the interstitial tissues are characterized by defects in tubular function. Papillary and tubular necrosis present with clinical symptoms due to an impaired ability to concentrate urine resulting in salt wasting, a decreased ability to excrete acid or defects in renal tubular absorption and secretion. Chronic stages will lead to glomerular involvement, resulting in proteinuria and hypertension. - URINARY TRACT INFECTIONS - Bacterial infection of the urinary tract is very common and constitutes a major medical problem. - The infecting organisms are usually the gram-negative intestinal bacilli, including Escherichia coli and, Pseudomonas aerogenesis, as well as Proteus, Klebsiella and Enterobacter species. Gram-positive organisms such as Streptococcus faecalis and Staphylococcus aureus are also implicated. These organisms are usually derived from the patient\'s own fecal flora. - Two routes of infection have been described: - Hematogenous - infection is blood-borne from the colon. - Ascending - infection is due to ascent of organisms from perineum to the urinary tract. This is the most common route. - Lower urinary tract infections can involve the urethra, the bladder or both. Upper urinary tract infections can involve the renal pelvis (pyelitis) - CYSTITIS - Lower urinary tract infections are characterized by dysuria and occasionally lower abdominal pain. The flushing action of urine outflow normally maintains a state of sterility in the bladder. Retention of urine favours bacterial growth and infection is more common in women due to the short urethra. Infectious prostatitis is the usual source of bladder infection in men. - **LIVER FUNCTION** - - **Objective** - The participants will be able to: - Describe The anatomy of liver? - Discuss the Maine liver the function in body. - Summary the significance role of LFT test in clinical diagnosis - Understanding pathophysiology disorder related to liver. - **What is the liver?** - An organ Shaped like a cone, dark reddish-brown that weighs about 3 pounds, located in the upper right-hand portion of the abdominal cavity, on top of the stomach, right kidney. - The liver is a unique organ due to its dual blood supply from the portal vein and the hepatic artery. - ![](media/image9.png)Anatomy of the liver ----------------------------------------- The liver consists of four lobes: the larger right lobe and left lobe, and the smaller caudate lobe and quadrate lobe. The left and right lobe are divided by the falciform ("sickle-shaped" in Latin) ligament, which connects the liver to the abdominal wall. The liver's lobes can be further divided into eight segments, which are made up of thousands of lobules (small lobes). Each of these lobules has a duct flowing toward the common hepatic duct, which drains bile from the liver. -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- - **Lobes**: The anatomical sections of the liver. - **Lobules**: Microscopic building blocks of the liver. (The foundation of the lobule is composed of hepatocytes) **.** - **[Function]** - The liver plays a role in nearly every organ system in the body. It interacts with the endocrine and gastrointestinal systems by aiding in digestion and metabolism. - Some of the more well-known functions include the [following:] - Production of bile, which helps carry away waste and break down fats in the small intestine during digestion. - Production of cholesterol and certain proteins for blood plasma (albumin, , protein C, protein S, and all the clotting factors of the intrinsic and extrinsic pathways) - Conversion of excess glucose into glycogen for storage. - Processing of hemoglobin for use of its iron content (the liver stores iron) - Conversion of poisonous ammonia to urea - Clearing the blood of drugs and other poisonous substances - Regulating blood clotting - Resisting infections by making immune factors and removing bacteria from the bloodstream - Clearance of bilirubin, also from red blood cells. - Fat-Soluble Vitamin Storage and/or Metabolism (vitamin A, E, K, B12, 25-hydroxylation for vitd3). **[Liver function test]** - Liver function tests are blood tests used to help find the cause of your symptoms and monitor liver disease or damage. The tests measure the levels of certain enzymes and proteins in your blood. - Liver function tests (also known as a liver panel) are blood tests that measure different enzymes, proteins and other substances made by the liver. - The different substances are often tested at the same time on a single blood sample, and may include the [following:] - [**Albumin**](https://medlineplus.gov/lab-tests/albumin-blood-test/)[,] a protein made in the liver. - **[Total protein](https://medlineplus.gov/lab-tests/total-protein-and-albumin-globulin-a-g-ratio/).** This test measures the total amount of protein in blood, which includes albumin and globulins. - [**ALP**](https://medlineplus.gov/lab-tests/alkaline-phosphatase/) (alkaline phosphatase), [**ALT**](https://medlineplus.gov/lab-tests/alt-blood-test/) (alanine transaminase), [**AST**](https://medlineplus.gov/lab-tests/ast-test/) (aspartate aminotransferase), and [**GGT**](https://medlineplus.gov/lab-tests/gamma-glutamyl-transferase-ggt-test/) (gamma-glutamyl transferase). These are enzymes that are mainly made by liver. Enzymes (are proteins that speed up certain chemical reactions in the body.) - [**Bilirubin**](https://medlineplus.gov/lab-tests/bilirubin-blood-test/), a waste product your body makes when it breaks down old red blood cells. - [**Lactate dehydrogenase (LDH)**](https://medlineplus.gov/lab-tests/lactate-dehydrogenase-ldh-test/), an enzyme found in most of the tissues, but some of the largest amounts are found in liver. ( is released into the blood when cells have been damaged by disease or injury) - [**Prothrombin time (PT)**](https://medlineplus.gov/lab-tests/prothrombin-time-test-and-inr-ptinr/), how long it takes your blood to clot. Prothrombin is a protein involved in blood clotting. It\'s made in liver. - **[Why are liver function tests done?]** - General symptoms of liver problems include: - [Hepatitis](https://medlineplus.gov/hepatitis.html) or have been exposed to hepatitis (swelling of the liver from infection or injury) - Lack of appetite - Nausea or vomiting - Weakness or feeling tired. - [Jaundice](https://medlineplus.gov/jaundice.html), a condition that causes skin and eyes to turn yellow. - dark urine or light-colored poop (less - common) - [Alcohol use disorder](https://medlineplus.gov/alcoholusedisorderaud.html) (AUD) - Diabetes - **[ALBUMIN]** - Albumin is made in the liver and it is the most abundant [protein](https://labtestsonline.org.uk/glossary/protein) in the blood [plasma](https://labtestsonline.org.uk/glossary/plasma)**,** Synthesized in the parenchymal cells of the liver - It keeps fluid from leaking out of blood vessels and carries [hormones](https://labtestsonline.org.uk/glossary/hormone), [vitamins](https://labtestsonline.org.uk/glossary/vitamin), drugs, and ions like [calcium](https://labtestsonline.org.uk/tests/calcium-test) throughout the body. - Albumin concentration in the blood is sensitive to liver damage. The concentration of albumin in the blood drops when the liver is severely damaged. - Serum albumin is low in liver failure. Because of its long half-life (2-3 weeks), albumin is most useful in the assessment of chronic liver failure. - Maintains oncotic plasma pressure and is involved in the transport of a wide variety of ligands and compounds found in the circulation. - Capable of binding toxic heavy metals and medicinal drugs. - Hypoalbuminemia is caused by liver disease, malnutrition, severe burns, inflammation, malabsorption due to inflammatory bowel disease, nephrotic syndrome. - Hyperalbumineuria is only important in cases of dehydration and severe diarrhea. - The total protein test is a rough measure of all the [protein](https://labtestsonline.org.uk/glossary/protein) in the plasma portion of blood. and not often requested in isolation. It can be used to calculate globulin; Proteins are important building blocks of all cells and tissues. - Total protein measures the combined amount proteins of the two major two classes of which are albumin and immunoglobulin. - Low total protein levels can suggest a liver disorder, a [kidney disorder](https://labtestsonline.org.uk/conditions/kidney-disease) ,. More specific tests, such as [albumin](https://labtestsonline.org.uk/glossary/albumin) and liver enzyme blood tests, must be performed to make an accurate diagnosis. - High total protein levels can indicate dehydration or some types of cancer, that lead to an accumulation of an abnormal protein (such as immunoglobulin in multiple myeloma). - Prolonged application of a tourniquet during blood collection can increase total protein levels. **[Alanine aminotransferase (ALT / GPT)]** - ALT is an enzyme that catalyzes the transfer of an amino group from alanine to the a-keto group of keto glutaric acid to generate pyruvic acid which is an important contributor to the citric acid cycle. - ALT is a more liver-specific enzyme. (ALT is a cytosolic enzyme that is found in high concentrations in the liver.) - elevated even before the clinical signs and symptoms of the disease appear.it used for Diagnosis and monitoring of liver disease associated with hepatic necrosis. - Alanine aminotransferase (ALT) activity is determined by a kinetic method using a coupled enzyme reaction where the rate of NADH consumption is measured at 340 nm. The NADH decrease is directly proportional to the ALT activity. - Patients with marked increase in amino transferase levels more than 10 times the upper normal limit typically have acute hepatic injury. - Moderate increases between 5-10 times the upper normal limit is suggestive of acute viral hepatitis. - In cases of acute viral hepatitis, ALT levels usually peak before jaundice appears and have a more gradual decrease. - Thereafter, whereas in ischemic injury ALT levels tend to decrease rapidly after peaking. - Viral hepatitis (A, B, C , D AND E) may be responsible for a marked increase in ALT levels. Although the increase associated with hepatitis C infection tends to be more modest than associated with hepatitis A or B. - Is an enzyme that is present in various tissues of your body. An enzyme is a protein that helps trigger chemical reactions that your body needs to function. - Aspartate aminotransferase (AST) is measured by a coupled enzyme kinetic method where the rate of decrease of NADH, determined at 340 nm, is directly proportional to the AST activity. - It used for Diagnosing and monitoring liver disease, particularly diseases resulting in a destruction of hepatocytes. - AST is found in the highest concentrations in liver, muscles, heart and kidney. AST is present in both cytoplasm and mitochondria of cells. - High levels of AST can be found in cases such as myocardial infarction, acute liver cell damage, viral hepatitis, poisoning. - Slight to moderate elevation of AST is seen in muscular dystrophy, dermatomyositis, acute pancreatitis, and crushed muscle injuries. - Very high concentrations of AST (more than 10 times the upper limit of normal (ULN)) are usually due to a rapidly developing liver disease [acute hepatitis](https://labtestsonline.org.uk/tests/acute-viral-hepatitis-testing), - Besides viral hepatitis very high levels (1000 u/l ) are associated with circulatory collapse and occasionally in extrahepatic obstruction. - **[Why is GPT mor sensitive than GOT?]** - AST It is not as sensitive or specific for the liver as ALT and elevation in AST may be seen as secondary to nonhaptic causes as well. - AST is present as cytosolic and mitochondrial isoenzymes and is found in the liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas, lungs, leucocytes, and red cells[.] - ALT is usually higher than AST in most types of liver disease in which the activity of both enzymes is predominantly from the hepatocyte cytosol. Hepatocellular injury and not necessarily cell death triggers the release of these enzymes into circulation. - ALT is a cytosolic enzyme that is found in high concentrations in the liver. The half-life of ALT is approximately 47 ± 10 hours. - **[Alkaline phosphatase (ALP)]** - ALP is an enzyme that is present in many parts of the body. But it is found in the liver, bones, intestine, and kidneys. - It used for Diagnosis and treatment of liver, bone, intestinal, and parathyroid disease, Determining the tissue source of increased alkaline phosphatase (ALP) activity in serum Differentiating between liver and bone sources of elevated ALP. - The activity of ALP found in serum is a composite of isoenzymes from those sites and, in some circumstances, placental or Regan isoenzymes. - Serum ALP is of interest in the diagnosis of 2 main groups of conditions: hepatobiliary disease and bone disease associated with increased osteoblastic activity. - Raised levels of ALP are usually due to a disorder of either the bone or liver. If other liver function tests such as bilirubin, GGT or ALT are also raised, this usually indicates that the ALP is coming from the liver. - However, if calcium and phosphate measurements are abnormal, this suggests that the ALP might be coming from bone. In some forms of liver disease such as hepatitis, ALP is usually much less elevated than AST or ALT. - GGT is a membrane localized enzyme found in high concentrations in the kidney, liver, pancreas, intestine, and prostate but not in bone. - This is an enzyme colorimetric method (rate method) where gamma-glutamyl transferase (GGT) transfers the gamma-glutamyl group of the substrate (L-gamma-glutamyl-3-carboxy-4-nitroanilide) to glycylglycine. - GGT is increased in most diseases that cause damage to the liver or bile ducts but is usually not helpful in distinguishing between different causes of liver damage as a single test. - The enzyme present in the serum appears to originate primarily from the hepatobiliary system, and GGT activity is elevated in all forms of liver disease. It is highest in cases of intra- or post hepatic biliary obstruction, reaching levels some 5 to 30 times normal. - Elevated levels of GGT are noted not only in the sera of patients with alcoholic cirrhosis but also in many sera from persons who are heavy drinkers. - Gamma-glutamyl transferase activity is inducible by drugs such as phenytoin and phenobarbital and, therefore, elevations should not be considered indicative of liver disease until drug use is ruled out. Elevations are also seen after ingestion of alcoholic beverages. - In liver disease GGT elevation parallels that of ALP and is very sensitive of biliary tract disease (biliary obstruction) - Measurement of this enzyme is also useful if jaundice is absent for the confirmation of hepatic neoplasms. - LDH is an enzyme with a very wide distribution throughout the body. - It is used for Investigation of a variety of diseases involving the heart, liver, muscle, kidney, lung, and blood. - Moderate elevations of total LDH levels are common in acute viral hepatitis and in cirrhosis, whereas biliary tract disease may produce only slight elevations. - In liver disease, elevations of LDH are not as great as the increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT). - Red blood cells contain much more lactate dehydrogenase (LDH) than serum. A hemolyzed specimen is not acceptable. - High serum levels may be found in metastatic carcinoma of the liver. - **[Bilirubin]** - Bilirubin is an orange-yellow pigment, a waste product primarily produced by the normal breakdown of haem**,** This bilirubin is initially water-insoluble bilirubin (unconjugated bilirubin), When bilirubin concentrations in the blood increase it leads to a condition called [jaundice](https://labtestsonline.org.uk/conditions/jaundice)**.** - After production in peripheral tissues, bilirubin is rapidly taken up by hepatocytes where it is conjugated with glucuronic acid to produce bilirubin mono- and diglucuronide, which are then excreted in the bile. - If the liver is not functioning correctly, the bilirubin will not be properly released (as bile). Therefore, if the bilirubin level is higher than expected, it may mean that the liver is not functioning correctly. - Bilirubin concentrations can be used to identify [liver disease](https://labtestsonline.org.uk/conditions/liver-disease) or to monitor the progression of [jaundice](https://labtestsonline.org.uk/conditions/jaundice) - bilirubin is not a sensitive or specific marker of liver function, so a careful interpretation of test results is necessary for accurate diagnosis. - Increased total or unconjugated(indirect ) bilirubin may be a result of [haemolytic](https://labtestsonline.org.uk/glossary/haemolytic), [sickle cell](https://labtestsonline.org.uk/tests/sickle-cell-test) or pernicious anemia\'s or ,If [conjugated (direct )bilirubin](https://labtestsonline.org.uk/glossary/conjugated-bilirubin) is elevated, there may be some kind of blockage of the liver or bile ducts, [hepatitis](https://labtestsonline.org.uk/conditions/hepatitis), trauma to the liver, [cirrhosis](https://labtestsonline.org.uk/conditions/cirrhosis), a drug reaction, or long-term alcohol abuse. - In newborns Excessive [unconjugated bilirubin](https://labtestsonline.org.uk/glossary/unconjugated-bilirubin) damages developing brain cells in infants (kernicterus) and may cause mental retardation, - Specimens should be protected from light and analyzed as soon as possible. - Grossly hemolyzed specimens should be rejected because hemoglobin inhibits the diazo reaction and falsely decreased results may be seen. - Conjugated hyperbilirubinemia has a high level of specificity for liver damage. - **Bilirubin Metabolism** ======================== - Heme, the substrate of bilirubin, is derived from red blood cells that have died. - Heme is degraded to biliverdin by heme oxygenase in the mononuclear phagocytes. - Biliverdin is subsequently reduced to bilirubin by biliverdin reductase. - Circulating bilirubin (insoluble) is bound to albumin and subsequently taken up by the hepatocytes. - To make it soluble, bilirubin undergoes conjugation, a reaction catalyzed by [bilirubin UDP](https://www.hepatitis.va.gov/provider/courses/livertests/livertests-glossary.asp#S1.9X)[glucuronyl transferase (UDPG)](https://www.hepatitis.va.gov/provider/courses/livertests/livertests-glossary.asp#S1.10X). - Conjugated bilirubin (soluble) is excreted into bile and reaches the bowel. - Bilirubin glucuronides are deconjugated by colonic bacteria and eliminated in the feces. Diagram of a diagram of a human body Description automatically generated **[Prothrombin time (PT )]** - Prothrombin is a protein made by the liver. Prothrombin helps blood to clot. The \"prothrombin time\" (PT) is one way of measuring how long it takes blood to form a clot, and it is measured in seconds (such as 13.2 seconds). - The coagulation pathway is made up of extrinsic, intrinsic, and common pathways. Prothrombin time is a coagulation test used to measure the integrity of the extrinsic and common coagulation pathways. - PT measures the rate of conversion of prothrombin to thrombin. Except for factor VIII, all other coagulation factors are synthesized by the liver. - The liver\'s function is crucial in coagulation. Suppose the synthetic function of the liver is normal and prothrombin time is delayed. This may indicate treatment with warfarin. - Severe liver injury leads to reduction of liver synthesis of clotting factors and consequently prolonged PT or an increased INR. - The levels of LFTs can point to the differentials. Many disease processes have very distinct abnormalities in the liver enzymes. Further investigation is warranted if repeated tests confirm abnormality. - **Alcohol** - In patients with alcohol use disorder, AST to ALT ratio is generally at least 2:1, showing a high level of AST activity in alcoholic liver disease Elevated GGT, along with AST, also suggests alcohol abuse. - **Medications** - Several medications are known to cause liver damage. Many of these are commonly used in daily practice, including but not limited to NSAIDs, antibiotics, statins, anti-seizure drugs, and drugs for tuberculosis treatment. - **Viral Hepatitis** - Viral illnesses are a common cause of hepatitis and elevation in LFTs. Viral hepatitis B, C, and D can cause chronic hepatitis, while hepatitis A and E cause acute viral hepatitis. Several other viruses, including HIV, Epstein-Barr (EBV), and Cytomegalovirus (CMV), can also cause hepatitis. - Autoimmune hepatitis is a chronic disease characterized by continuing hepatocellular inflammation, necrosis, and a tendency to progress to cirrhosis. The patient usually presents with high LFTs without apparent cause. These patients can have positive autoantibodies, including antinuclear antibodies, anti-smooth muscle antibodies, anti-liver/kidney microsomal antibodies, and antibodies to the liver antigen. - **Cirrhosis** - Cirrhosis is a clinical condition in which scar tissue replaces normal, healthy liver tissue, it blocks the flow of blood through the organ and prevents the liver from functioning properly. - Signs and symptoms appear like fatigue, nausea, weight loss, jaundice, bleeding from the gastrointestinal tract, itching and swelling in the legs and abdomen. Symptoms may not appear until the liver is badly damaged**.** - Causes of cirrhosis could be form: Chronic hepatitis C infection, Blocked bile ducts, Drugs, toxins, and infection. - **[Questions]**? [The best liver function enzyme test is:] a\. AST/ALT b\. Alkaline phosphatase c\. Bilirubin d\. INR [In liver failure, the prolonged INR improves with vitamin K administration]. a\. True b\. False [In a patient with chronic liver disease, all of the following suggest the presence of chronic liver insufficiency, except:] a\. Low albumin b\. Prolonged prothrombin time c\. Elevated bilirubin d\. Elevated aminotransferases e\. Thrombocytopenia [AST has a wide \-\-\-\-\-\-- distribution]. a.Tissue b\. Cardic c.Renal d.Blood \-\-\-\-\-\-\-\-\--[is a group of enzyme found mainly in bone,liver,intestines , placenta]. a.AST b.ALT C.GPT d.ALP \-\-\-\-\-\-\-\-\--[is a group of enzyme found mainly in bone,liver,intestines , placenta]. a.AST b.ALT C.GPT d.ALP **Pancreas enzyme** - **Objective** - The participants will be able to: - Describe The anatomy of Pancreas? - Discuss the Maine Pancreas endocrine and exocrine function in body. - List common useful analyte that helps in pancreatic diseases diagnosis - Explain test importance and expected results. - **[What is a pancreas?]** - The pancreas is an elongated, tapered organ located across the back of the belly, behind the stomach. The pancreas is part of the gastrointestinal system. - **[Anatomy of Pancreas:]** - The pancreas anatomy includes: - Head: The wider part of the pancreas that sits in the curve of your duodenum. - Neck: The short part of the pancreas extending from the head. - Body: The middle part of the pancreas between the head and neck, which extends upward. - Tail: The thinnest part of the pancreas, located near your spleen. ![https://teachmephysiology.com/wp-content/uploads/2018/04/The-Exocrine-and-Endorine-Pancreas.jpg](media/image12.jpeg) [Functions of the pancreas] --------------------------------------- The pancreas is made up of 2 types of function (glands): - **Exocrine function. **The exocrine gland secretes digestive enzymes. These enzymes are secreted into a network of ducts that join the main pancreatic **duct**. This runs the length of the pancreas. - **Endocrine function. **The endocrine gland, which consists of the islets of Langerhans, secretes hormones into the **bloodstream.** - **[The pancreas has digestive and hormonal functions:]** - The enzymes secreted by the **exocrine** gland are important to digestion. - These enzymes travel down the pancreatic duct into the bile duct in an inactive form. When they enter the duodenum, they are activated. - The exocrine tissue also secretes a bicarbonate to neutralize stomach acid in the duodenum. - These enzymes **exocrine** include **trypsin** and chymotrypsin to digest proteins; **amylase** for the digestion of carbohydrates; and **lipase** to break down fats. - The main **hormones** secreted by the **endocrine** gland in the pancreas are **insulin** (lower blood sugar) and **glucagon** (raise blood sugar), which regulate the level of glucose in the blood, and somatostatin, which prevents the release of insulin and glucagon. - **[Endocrine gland hormones]** - **Insulin:** - Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. - Insulin is an anabolic hormone that promotes glucose uptake, glycogenesis, lipogenesis, and protein synthesis of skeletal muscle and fat tissue. - Dysfunction of insulin production & secretion, as well as the target cells' responsiveness to insulin, can lead to diabetes mellitus. - Metabolic actions of insulin help to maintain glucose homeostasis and promote glucose utilization. - Insulin increases glucose utilization in peripheral organs (e.g., skeletal muscle and adipose tissue) and suppresses hepatic glucose production (HGP) and adipose tissue. - It decreases plasma glucose levels by increasing the transport entry of glucose in muscle and adipose tissue by way of nonspecific receptors. - **Glucagon:** - Glucagon is a peptide hormone secreted from the alpha cells of the pancreatic islets of Langerhans. - The most potent regulator of glucagon secretion is circulating glucose. Hypoglycemia stimulates the pancreatic alpha cell to release glucagon and hyperglycemia inhibits glucagon secretion. - Glucagon stimulates the liver to convert its stores of glycogen back into glucose (glycogenolysis). - It promotes the production of glucose from amino acid molecules in liver. This process is called (gluconeogenesis). - Glucagon stimulates glycerolipolysis, the breakdown of stored triglycerides liver converts glycerol into glucose. - **[Exocrine gland enzymes]** - **Lipase** - Lipase is an [enzyme](https://labtestsonline.org.uk/glossary/enzyme) manufactured primarily by the pancreas. It is released into the duodenum to help digest fatty foods. - The main function of lipase enzymes is the hydrolysis of fats. It catalyses the breakdown of triglycerides into fatty acids and glycerol. - When pancreatic cells are inflamed as in pancreatitis or when its path into the duodenum is blocked, increased amounts of lipase pass into the blood. - A lipase test may be used if you show symptoms of a pancreatic disorder, such as severe abdominal pain, fever, loss of appetite, or nausea and to monitor the effect of treatment. - In acute [pancreatitis](https://labtestsonline.org.uk/conditions/pancreatitis), lipase concentrations are very high, often 2 to 5 times normal. - Slightly high lipase values may occur in other conditions such as [kidney disease](https://labtestsonline.org.uk/conditions/kidney-disease), salivary gland inflammation, or [peptic ulcer disease](https://labtestsonline.org.uk/conditions/peptic-ulcer). - **[Amylase]** - Amylase is an [enzyme](https://labtestsonline.org.uk/glossary/enzyme) made mainly by the pancreas. It is released from the pancreas into the digestive tract to help digest starch in our food. - It is usually present in the blood in small quantities. When cells in the pancreas are injured or if the pancreatic duct is blocked increased amounts of amylase find their way into the bloodstream. - Serum amylase is secreted in specific isoforms by the salivary glands (**s-amylase**) and pancreas (**p-isoamylase**). It predominantly acts to digest starch, glycogen, and related polysaccharides. Almost all laboratories currently measure total serum amylase. - The blood test for amylase is used to diagnose acute pancreatitis (inflammation of the pancreas) and other pancreatic diseases. - An amylase test may be requested if you show symptoms of a [pancreatic disorder](https://labtestsonline.org.uk/conditions/pancreatic-diseases), such as severe abdominal pain, fever, loss of appetite, or nausea. - In pancreatitis, which is a severe inflammation of the pancreas, amylase concentrations are usually very high, often 5-10 times normal. - Pancreatic amylase may be elevated due to pancreatitis as well as other conditions in which pancreatic amylase is released (eg, cannulation of the pancreatic duct) - **[Trypsin]** - Trypsin is an [enzyme](https://www.healthline.com/health/why-are-enzymes-important) that helps us digest protein. In the small intestine - Trypsin is produced by the [pancreas](https://www.healthline.com/human-body-maps/pancreas) in an inactive form called **trypsinogen**. The trypsinogen enters the [small intestine](https://www.healthline.com/human-body-maps/small-intestine) through the common bile duct and is converted to active trypsin. - This active trypsin acts with the other two principal digestive proteinases --- [pepsin](https://www.healthline.com/human-body-maps/stomach-cross-section) and [chymotrypsin](https://www.healthline.com/nutrition/proteolytic-enzymes) --- to break down dietary protein into peptides and amino acids. - Trypsin is an optimal marker for detecting changes in the physiological state of the pancreas because it is specific for this organ. It has been established that trypsin administration into the blood decreases enzymes output with pancreatic juice. - **[Chymotrypsin]** - Chymotrypsin is a digestive enzyme that promotes proteolysis, or the breakdown of proteins and polypeptides. - It is a [serine](https://pubchem.ncbi.nlm.nih.gov/compound/serine) protease synthesized in the pancreas and is a vital component in the pancreatic juice. Like most proteolytic enzymes, chymotrypsin is activated from its inactive zymogen precursor, chymotrypsinogen, - Chymotrypsin is the most abundant pancreatic protease that represents up to 10-20% of the total protein synthesized by the exocrine pancreas. - **[Pancreatitis]** - Pancreatitis is the redness and swelling (inflammation) of the pancreas. Is inflammation of the pancreas that progresses over time and leads to permanent damage. - **Acute pancreatitis** is a sudden inflammation, lasts for a short time, and may cause serious problems or be deadly in severe cases. - **Chronic pancreatitis** is a long-lasting inflammation that comes and goes over time, causes permanent damage to the pancreas, often causes scarring of pancreatic tissue. - Symptoms of pancreatitis may include Severe abdominal pain, Nausea and vomiting, Loss of appetite, Fever, and Back pain. - The most common cause is persistent and heavy alcohol use. - Serum concentrations of amylase and lipase rise within hours of the pancreatic injury. A threshold concentration 2--4 times the upper limit of normal is recommended for diagnosis. - **[Lipase or amylase for the diagnosis of acute pancreatitis?]** ============================================================================ - Serum lipase is the preferred test for diagnosing acute pancreatitis, since it is more sensitive than serum amylase, just as specific, rises more quickly, and remains elevated longer. thus, allowing it to be a useful diagnostic biomarker in early and late stages of acute pancreatitis. - Serum lipase typically increases 3--6 hours after the onset of acute pancreatitis and usually peaks at 24 hours. - Unlike amylase, there is significant reabsorption of lipase in the renal tubules, so the serum concentrations remain elevated for 8--14 days. This means it is far more useful than amylase when the clinical presentation or testing has been delayed by more than 24 hours. - Serum lipase also has a greater sensitivity than amylase in patients with alcoholic pancreatitis. - Amylase has a short half-life of 12 hours so the concentration can normalize within 24 hours. This significantly reduces its value as a diagnostic test relatively early in the clinical course. **Module 2** **Lipid metabolism** - **[Objective]** - - - - - **[Learning Activities]** - Connection Activities: - **[Ask Participants:]** - Are you satisfied with your profession? - How do you feel about being a Medical Technologist? - What are the challenges to our profession? - Ask participants about their knowledge of Lipids, what do they know about it? - Ask participants to discuss types of lipids? - Some basic facts - Functions - Composition - **[Ask participants to discuss:]** - Sample requirements of lipid test. - Sample acceptability. - Identifying Normal and abnormal results - Ask groups to present their discussion points (3 minutes to each group) - Flip Chart - Past experiences - **[Learning methods/Activities]** - PowerPoint slides - Instructor-Led Learning - Case studies and brainstorming - Group discussion. - Flip Chart Demos - Illustrative images - Role Playing - Related Materials - Practical illustrations - CAP Checklists - **Introduction: What are the lipids?** - The lipids are a large and diverse group of naturally occurring organic compounds. - Lipids are carbon and hydrogen containing compounds that are very hydrophobic (insoluble in water). - Lipids are easily stored in the body. They serve as a source of fuel and are an important constituent of the structure of cells. - Biologically important groups of lipids are neutral fats (**triglycerides**), conjugated lipids (**phospholipids** and glycolipids) and the sterols (**cholesterol**). - The major lipid components found in the blood are triglycerides, cholesterol and phospholipids. They exist and are transported in the blood as **lipoproteins**. **Types of lipids** - **Triglyceride:** - Triglycerides are usually three fatty acids esterified to a single glycerol molecule. Stored as adipose tissue they provide a source of readily available energy (they may be converted to glucose) - Triglycerides can be either dietary (exogenous) or synthesized in the liver (endogenous). They constitute 95% of fats stored in tissues. - Triglycerides are transported mostly in the form of large lipoproteins called **chylomicrons** and **VLDL.** - High triglycerides increase the risk of heart disease, high blood pressure and high blood sugar. - **Causes of high triglycerides:** In many cases, habitual overeating causes high triglycerides. Occasionally, the trigger is an underlying condition such as: - Excessive alcohol consumption - Adverse side effect of medications - Poorly managed diabetes - [Hypothyroidism](https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/thyroid-hypothyroidism) (insufficient production of thyroid hormones) - Some types of [liver disease](https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/liver) - Some types of [kidney disease](https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/kidney-disease) - Some [genetic disorders](https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/genetic-conditions), including the inherited disease familial hypertriglyceridemia and familial combined hyperlipidemia (triglyceride and LDL are both elevated). - **Cholesterol:** - **Cholesterol** is a fat-like, waxy substance, an unsaturated sterol (steroid alcohol) of high molecular weight. - It is used for the manufacture and repair of all membranes, for synthesis of bile acids and vitamin D and is the precursor for steroid hormones (e.g. sex hormones). - The body\'s source can be dietary or liver synthesis. 70% of the body\'s cholesterol is stored in the skin, adipose tissue and muscle cells. The remaining 30% is transported in the blood as lipoproteins -- mostly **LDL** and **HDL**. **Causes of high cholesterol levels:** - Unhealthy diet: frequent eating saturated fat or trans-fat rich diets, such as fatty meat. - Inactivity: Continuous sitting idle or sedentary lifestyle increases LDL cholesterol levels in blood vessels. - [Obesity](https://www.narayanahealth.org/blog/obesity-is-the-new-silent-killer/): A higher body mass index (BMI) increases the risk of high cholesterol. - Medical conditions: Various illnesses cause an increase in LDL levels, including lupus, HIV infection, diabetes, chronic kidney disease, and hypothyroidism. - Medications: Medicines for other health issues can increase cholesterol levels, such as acne and AIDS. - Smoking and alcohol: Tobacco abuse and too much alcohol consumption increases total cholesterol level and decreases HDL levels. - Gender (women's risk for high cholesterol increase after post menopause) - Family history and age Cholesterol in the blood stream **What is the correlation between heart disease and cholesterol?** - Cholesterol is a fat-based substance and doesn't dissolve with blood. - When the cholesterol level increases, it starts building up in the wall of the arteries. This buildup of c

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