Week 1: Fluids, Electrolytes and Metabolism PDF

**[Week 1: Fluids, Electrolytes ad Metabolism ]** **Fluids and electrolytes** **Body fluids** - Water accounts for \~ volume of body fluids - Normal amounts of water in human body. - Women= 55% - Men= 60% - Women have more adipose, therefore less water   **Distribution of...

**[Week 1: Fluids, Electrolytes ad Metabolism ]** **Fluids and electrolytes** **Body fluids** - Water accounts for \~ volume of body fluids - Normal amounts of water in human body. - Women= 55% - Men= 60% - Women have more adipose, therefore less water   **Distribution of water** - **Intracellular fluid (ICF)** - Inside cells (25L) - 2/3 of body fluids - 40% of body weight - **Extracellular fluid (ECF)** - Outside cells (15L) - Interstitial fluid, PLASMA, lymph etc - Plasma - Link between intra and extracellular environments - Water is continually exchanged through capillary walls and cell membranes by osmosis   Water is a universal solvent - For **2** types of **solutes** - **Electrolytes**: chemicals that dissociate into free ions (charged) - Na^+^ (cations), Cl^-^ (anions) - **Non- electrolytes:** Chemical bonds prevent dissociation, no charge - Glucose, lipids, creatinine, urea   **Electrolyte pattern is distinct** - Extracellular - Sodium main cation (dominant electrolyte to plasma osmolarity) - Intracellular - Potassium main cation (dominant electrolyte to intracellular osmolarity)   **Sodium and potassium pump** - Maintains these concentrations using active transport (ATP, thus oxygen is required)   - **Despite these electrolyte differences the osmolarity of ECF and ICF is the same** - There for so is the water concentration               **Water balance** - Water intake (2.5L) = water output (2.5L) - Sources for water intake - Food and fluids - Metabolic processes (200ml) making ATP   **Dehydration** - Thirst is driving force - Osmoreceptors In hypothalamus detect increases in plasma osmolarity (decrease saliva) - Requires action of angiotensin II and antidiuretic hormone (ADH) to accentuate thirst and reduce urinary loss of water - Dehydrated= lowers blood volume   Sources for water output - Faeces - Expired air from lungs - Cutaneous transpiration - Sweat - Urine production - Kidneys are the major regulators of body fluid composition - Tubular reabsorption of water and electrolytes regulated by hormones - ADH, Aldosterone, Angiotensin, ANP     **Acid-Base balance of blood** **pH** - Relative concentration of hydrogen ions (H^+^) - Blood pH = 7.35 to 7.45 (enzymes are pH sensitive) - H^+^ originates from metabolism (lactic acid, carbonic acid) and ingested nutrients (fatty acids, amino acids) - Above 7.45=alkalosis - Less than 7.35=acidosis   **pH is maintained by** 1. Buffers 2. Lungs (CO~2~ and H~2~O) 3. Kidneys (H^+^ and HCO~3~^\_^)   **Buffers** - Chemicals that can regulate pH - Prevent dramatic changes in hydrogen concentration - Act instantaneously - Binds to Hydrogen when pH drops - Releases hydrogen when pH rises - Composed of weak acid (H+ donor) and a weak base (H^-^ acceptor) **Major chemical buffers** 1. **Protein buffer system (ICF)** - **Protein buffer system** - **Amino acids can act as a weak acid or base** - **Release H^+^ acid group or bind to H^+^ amine group** - **R group most buffering** - **Chemical buffer system** - **Can tie up excess acids or bases but on the LUNGS and KIDNEYS can eliminate them from the body** 1. **Bicarbonate buffer system (ECF; Plasma)** - Mix of carbonate H~2~CO~3~ (acid = H^+^ donor) and bicarbonate HCO~3~- (base = H^+^ acceptor) - Carbonic acid concentration is regulated by **RESPIRATION** - Bicarbonate ion concentration is regulated by **KIDNEYS** - Bicarbonate is how we transport CO2 around the body - We use this equation to buffer our blood (reversible chemical reaction)             - - - - - - - - 1. **Phosphate buffer system (CSF and urine)** - Kidneys remove ultimate pH regulatory organs - Remove all METABOLIC acids (non-CO2) - Sole regulators of alkaline substances (HCO~3~-) - Tubular secretion or reabsorption of bicarbonate ions (HCO~3~-) or generate new bicarbonate ions if necessary - Takes hours to days to restore pH - Hydrogen ions retained by tubular reabsorption - Bicarbonate ions excreted (tubular secretion) - Hydrogen ions excreted, or neutralised by HCO~3~- - Bicarbonate ions reabsorbed - Thus, urine pH varies (4.5-8.0) - Lungs and kidneys work together     **Metabolism** - Chemical reactions necessary to maintain life (enzymes required) - Catabolism - Food broken down into the building blocks - Energy released is used to make ATP - Anabolism - Molecules are built from the building blocks - ATP is required - Anabolism = catabolism = weight stable   - Water soluble building blocks are absorbed through the jejunum wall into capillaries of the villi - Where transported to liver via hepatic portal vein - Lipids are absorbed into lacteal of villi (lymphatic system)     **Hepatic portal system** - Connects capillary beds of digestive tract with the capillary beds of liver - Liver receives blood from stomach, intestines, pancreas and spleen for inspection - Blood then collected into hepatic veins which empty into inferior vena cava           **Liver anatomy** - Lobes composed of 100,000\'s of hexagonal lobules (cylinders) - Lobules supported by scaffold of reticular connective tissue - Lobules composed of plates of cuboidal hepatocytes radiating out from a central vein - Plates separated by blood filled channels (sinusoids) lined with fenestrated epithelial cells - Blood from hepatic portal vein (70%) and hepatic artery (30%, O~2~) percolates sinusoids    **[Hepatocytes]** - Absorb nutrients for metabolism or storage - Remove, degrade, detoxify (SER) - Hormones, toxins, MEDICATIONS - Kupffer cells (macrophages) remove damaged erythrocytes and microorganisms - Synthesise and secrete - Plasma proteins, clotting factors - Cholesterol (85%) - Bile (bile salts, pigments, excess cholesterol) - Angiotensinogen - Vitamin (a, D, E, K) and mineral (Fe) storage - Major role in maintaining blood glucose - 4 to 8 mmols/ L of blood - Glycogenesis - Production of glycogen from glucose - Glycogenolysis - Hydrolysis ([splitting]) of glycogen to release glucose - Gluconeogenesis - [New] glucose produces from lipids and amino acids - Synthesise lipoproteins - Transport cholesterol and fatty acids in blood - Coat of proteins and phospholipids (more protein =higher density) **[Lipoproteins ]** 1. **Very low-density lipoproteins (VLDL)** - **Transport triglycerides to adipose, then become LDL** 2. **Low density lipoproteins (LDL)** - **Transport cholesterol TO cells (and arteries)** - **LDL absorbed by cells that need cholesterol** 3. **High density lipoproteins (HDL)** - **Transport cholesterol FROM CELLS (and arteries) back to liver for elimination in bile** **Production of ATP** - Glucose is the catabolic breakdown product of carbohydrate digestion - Glucose is used to make ATP - Energy is released in a series of small steps - Energy produced adds a phosphorus to ADP to make 32 ATP from one glucose         **[Three major pathways ]** 1. **Glycolysis** - **In cytosol** - **Glucose broken down to two pyruvates** - **Creates 2 ATP, NADH (coenzyme** 1. **Anaerobic fermentation (without oxygen)** - **In cytosol** - **Pyruvate converted to lactic acid (and NAD^+^), which allows glycolysis to continue**         1. **Aerobic respiration (With oxygen)** - Pyruvate enters mitochondria matrix - Undergoes the citric acid (Krebs) cycle - Carbons stripped away and lost as 6 CO~2~ - 2 ATP, NADH, FADH~2~ - NADH and FADH~2~ enter the electron transport chain across inner mitochondrial membrane - Generates ATP in series of small steps - Oxygen final electron acceptor, generating H~2~O - ATP synthase generates 28 ATP     **Lipid metabolism (hepatocytes)** - Lipids broken down to acetic acid, which enter citric acid cycle - Process fast, often incomplete - Results in **ketoacidosis** from accumulation of **acetoacetic acid** and **acetone** (sweet breath)   **Protein metabolism (hepatocytes)** - Shifts amino groups (NH~2~) between molecules - Amino acids can be - Converted to glucose or fat - Used for mitochondrial ATP production - Synthesis of non-essential amino acids   Amino acid deamination - [Removed amino groups] can be lost as ammonia - Hepatocytes converts ammonia to urea which is excreted in urine   [Thermoregulation] - During the process of generating ATP, 60% of energy lost as heat - Basic metabolic rate is the amount of heat produced by the body (60 to 72 kcal/hour) - Thyroxine is most important control factor   [Body temperature] - Normal core is 36-37.5C˚ - 3D structure and function of enzymes (protein) - Blood is major agent of heat exchange between core and shell - Core temp remains relatively constant, while shell temp fluctuates substantially (20-40C˚)   Thermostat in hypothalamus - Receives sensory information from: - Peripheral thermoreceptors (skin) - Central thermoreceptors (hypothalamus, blood) - Initiates appropriate heat gain or loss-promoting mechanisms