Gastrointestinal Physiology and Metabolism

Question 1

describe the 4 different types of secretory glands associated with the gastrointestinal tract

Answer 1

1. Single cell mucous glands – e.g. goblet cells. Produce mucous in response to epithelial irritation
2. Pit glands – e.g. crypts of Lieberkuhn. contain both goblet cells and enterocytes, which are specialised secretory cells producing digestive enzymes such as sucrose, maltase and enteropeptidase.
3. Tubular glands – e.g. oxyntic glands. These branched glands are found in the stomach and are composed of several different cells which produce multiple secretions in response to food
4. Complex glands – e.g. salivary glands. These lie outside the walls of the gastrointestinal tract and are composed of both acinar and ductal epithelial cells. The acini are lined with 3 different types of glandular cells whose primary secretions are modified by the ductal epithelium en route to the gastrointestinal tract.

Question 2

describe the effect of increased parasympathetic activity on salivary gland function

Answer 2

increased acinar synthesis/secretion
increased ductal epithelial transport
increased blood flow via VIP, ACh
increased contraction of acinar myoepithelial cells

rapid flow of enzyme-rich saliva

Question 3

Outline bilirubin metabolism and excretion

Answer 3

it is a breakdown product of haemoglobin

transported in the blood bound to albumin

conjugated to glucuronic acid in liver to form bilirubin glucuronide which is excreted into bile canaliculi and ducts

Intestinal bacteria then convert conjugated bilirubin to urobilinogen

circulating urobilinogen = urobilin
intestinal urobilinogen = stercobilin

Question 4

Outline how bile secretion is controlled

Answer 4

The mixture is secreted into the bile canaliculi to the common hepatic duct and then stored and concentrated in the gall bladder.
The presence of fatty acids in the duodenum after a meal stimulates CCK release from I cells which induces gall bladder contraction, relaxation of the sphincter of Oddi, and emptying of bile into the intestine via the common bile duct.

Question 5

Describe the functions of bile salts

Answer 5

bile salts act as a detergent to decrease surface tension and promote emulsification of fat particles, creating a large surface area for the action of lipases.

Bile salts then combine with lipid digestion products (monoglycerides, free fatty acids) to form micelles

Micelle formation is necessary for efficient fat absorption since it maintains a large surface area for lipid diffusion across the mucosal epithelium.

Question 6

what is jaundice and describe the three forms of jaundice

Answer 6

Jaundice occurs due to elevated levels of plasma bilirubin leading to yellow discolouration of the eyes, skin and mucous membranes

1. Pre-hepatic jaundice:
   - due to haemolysis
   - excess bilirubin production
   - increased levels of circulating bilirubin
   - e.g. sickle cell anaemia, haemolytic disease of the newborn
2. Hepatic:
   - inability of liver to conjugate/excrete bilirubin
   - e.g. hepatitis, alcoholic liver disease
3. Post-hepatic:
   - obstruction of bile duct
   - e.g. gallstones, pancreatic carcinoma

Question 7

Explain the role of epithelial digestive enzymes

Answer 7

The cells of the intestinal mucosa also play an important digestive function, particularly in relation to carbohydrates. Oligosaccharides and polypeptides are present in the small intestine as a result of carbohydrate digestion by pancreatic α-amylase and protein digestion by pepsin/proteases. However, the intestine is unable to absorb these and further digestion is necessary to produce monosaccharides and amino acids. This is mediated by oligosaccharidases and peptidases which are bound to enterocytes of the crypts of Lieberkuhn covering the epithelium of the intestinal brush border with their active sites exposed to the luminal contents.

oligosaccharidases digest monosaccharides;

peptidases digest amino acids

Question 8

Describe how the small intestine is specialised for absorption

Answer 8

The luminal surface of the small intestine is suitably adapted for absorption by possessing both specific transport mechanisms and a large surface area

Increase absorptive SA:

• mucosa - into macroscopic folds which project up into lumen.
• Microscopic mucosal projections, known as villi, which contain their own blood supply and lacteal.
• Folding of the epithelial membrane produces numerous microvilli, giving rise to the term epithelial brush border

Question 9

Outline the absorption mechanisms for carbohydrates

Answer 9

Carbohydrates absorbed as monosaccharides (glucose, galactose, fructose)

Absorption of glucose and galactose occurs via secondary active transport, energy being provided by the Na+/K+ ATPase on the basolateral membrane. The process is Na+-dependent and relies on a Na+ co-transport carrier molecule in the luminal epithelial membrane to move monosaccharides against the concentration gradient.

In contrast, fructose absorption across the apical membrane occurs by facilitated diffusion. This requires a diffusion gradient from the intestinal lumen into the epithelium, the carrier molecule (GLUT5) simply acting to decrease the diffusion barrier created by the fatty cell membrane.

high intracellular concentrations of monosaccharides generated during absorption generate the concentration gradients required for these nutrients to diffuse across the basolateral membrane into the mucosal capillaries. For all monosaccharides, this process occurs via facilitated diffusion linked to a carrier protein (GLUT2) to increase the rate of transport through the lipid membrane.

see lecture 4 for diagram

Question 10

Outline the absorption mechanisms for proteins

Answer 10

Proteins absorbed as short peptides and amino acids via secondary active transport

using an H+ co-transport system

H+ gradient across the apical membrane is created by a luminal Na+/H+ exchanger, the energy for the process being provided by the Na+/K+ ATPase on the basolateral membrane

Several specific carrier molecules are required to link H+ movement to transport of different peptides and amino acids

Absorbed short peptides are then degraded by intracellular peptidases before transport of amino acids across the basolateral membrane into the mucosal capillaries occurs via facilitated diffusion.

see lecture 4 for diagram

Question 11

Outline the absorption mechanisms for lipids

Answer 11

see lecture 4 for diagram

Question 12

Outline the absorption mechanisms for sodium and water

Answer 12

see lecture 4 for diagram

Question 13

Outline the absorption mechanisms for lipids

Answer 13

see lecture 4 for diagram

Pancreatic lipase hydrolises triglycerides to form fatty acids and monoglycerides

these are Transported to epithelial border in micelles

Monoglycerides, FFAs enter the epithelial membrane by diffusion at the apical membrane

Monoglycerides and free fatty acids are then reconstituted into triglycerides by intracellular enzymes before being taken up by the endoplasmic reticulum and packaged within a lipoprotein coat to form chylomicrons

leave the mucosal epithelium through the basolateral lateral membrane via exocytosis, but as they are too large to enter the mucosal capillaries they pass into the intravillous lymphatics (lacteals).

then returned to the blood via the lymphatic system

Micelles recycled to ferry more lipid

Question 14

Outline the absorption mechanisms for sodium and water

Answer 14

see lecture 4 for diagram

Water:

• mostly osmosis
• Dilute chyme which decreases intestinal osmolarity and therefore favours absorption of water

Sodium:

• primary active transport of Na+ out of the epithelial cells (via a Na+/K+ ATPase on the basolateral membrane) into the paracellular space between adjacent cells is followed by electrostatic diffusion of Cl-
• this creates an osmotic gradient in the paracellular space and therefore water moves in via osmosis
• less Na+ in the cell so Na+ from intestine moves in via facilitated dissuasion
• Movement of Na+ and H2O into the paracellular space elevates hydrostatic pressure and fluid is forced out into the interstitium
• this helps absorption into mucosal cellsmutual dependence of Na+ and nutrient absorption

Question 15

Outline the absorption mechanisms for vitamins

Answer 15

see lecture 4 for diagram

FAT-SOLUBLE VITAMINS (A, D, E & K):
- absorbed with fats in which they are dissolved

WATER-SOLUBLE VITAMINS (e.g. C, B2, Folic acid):
- generally diffuse across intestinal mucosa if taken in sufficiently high doses

VITAMIN B12:

• needs intrinsic factor which comes from parietal cells
• Intrinsic factor binds to vitamin B12 in the intestine
• forms a dimer
• protective against digestion and allows binding to the epithelial cell membrane receptor
• Vitamin B12 dissociates from intrinsic factor within the cell and is carried in the blood bound to transcobalamin II

Question 16

Outline the absorption mechanisms for calcium

Answer 16

see lecture 4 for diagram

• requires vitamin D - can get from diet and skin
• regulated by parathyroid hormone
• Parathyroid hormone promotes renal activation of vitamin D
• increases levels of Ca2+ binding protein in the mucosal epithelium
• increases activity of the Ca2+ ATPase in the basolateral membrane
• increasing intestinal Ca2+ absorption
• The activity of parathyroid hormone is inhibited by elevated plasma Ca 2+ levels thereby providing negative feedback regulation of intestinal Ca2+ absorption.

Question 17

Outline the absorption mechanisms for iron

Answer 17

see lecture 4 for diagram

• ferrous (Fe2+), rather than ferric (Fe3+), ions are absorbed
• relies on binding to a transport protein, known as transferrin
• Fe2+-transferrin complex then binds to an epithelial membrane receptor
• passes into the cell by endocytosis
• inside the mucosal epithelium, the Fe2+ is released from transferrin as is absorbed into the circulation, where it becomes bound to plasma transferrin.
• In iron deficiency (e.g. following blood loss) the ability to absorb iron is increased, with an increased density of membrane receptors for the iron-transferrin complex.

Question 18

what can deficiency in vitamin B12 cause

Answer 18

Deficiency of vitamin B12 most commonly results from pernicious anaemia, an autoimmune disease in which antibodies are produced against parietal cells leading to intrinsic factor deficiency and malabsorption of vitamin B12.

Question 19

Define metabolism and metabolic rate

Answer 19

Metabolism = Sum of
CATABOLIC + ANABOLIC pathways

Sum of all chemical processes involved in:

• Producing energy from exogenous (eg food) and endogenous (eg glycogen) sources
• Synthesising and degrading structural and functional tissue components
• Disposing of resultant waste products

Conversion of chemical energy to other forms of energy

Question 20

Define energy balance and describe situations that affect it

Answer 20

In the steady state INPUT OF FOOD = OUTPUT OF WORK/HEAT

Input of food is balanced against the output of work and heat generated in support of key metabolic processes, such as:

(1) mechanical work of muscle contraction, cell movement
(2) synthetic reactions required for fuel storage, tissue building, generation of essential functional molecules;
(3) membrane transport - minerals, ions and amino acids;
(4) generation and conduction of electrical, chemical and mechanical signals;
(5) heat production for temperature regulation and as a result of inefficient chemical reactions; and
(6) detoxification and degradation

POSITIVE ENERGY BALANCE needed in childhood, pregnancy, post-illness/trauma

Question 21

Describe mechanisms that influence energy intake

Answer 21

regulated by hypothalamus

• lateral nuclei of the hypothalamus - house the main feeding centre, stimulation of which increases the desire for food
• ventromedial nuclei serve as the satiety (feeling full) centre - if this stimulated - inhibits the feeding centre

two distinct types of neurons in the arcuate nuclei:

1. proopiomelanocortin (POMC) neurons:
   - which secrete (alpha)-melanocyte-stimulating hormone ((alpha)-MSH) and cocaine- and amphetamine-related transcript (CART)
   - reduce food intake
2. orexigenic neurons:
   - secrete neuropeptide Y (NPY) and agouti-related protein (AGRP)
   - increase food intake

Short term regulation:

• nutrient related signals:
• decreased glucose/FFAs = increased food intake
• increased cholecystokinin (CCK) / glucagon-like peptide-1 (GLP-1) = decreased food intake
• GI distension = vagal inhibitory signals = decreased desire for food

Long term regulation:

• sensing of energy stores:
• increased leptin/insulin = decreased food intake
• Overfeeding = positive energy balance = less reward for food, increased satiety (fullness), decreased food intake
• Energy deprivation = negative energy balance = more reward for food, decreased satiety, increased food intake

Question 22

what is the equation for BMI, and what are healthy, overweight and obese values

Answer 22

weight in kg divided by height in m2

• BMI between 20 and 25 = healthy
• clinical terms a BMI of 25-30 = overweight
• > 30 = obese

Question 23

what is the equation for BMI, and what are healthy, overweight and obese values

Answer 23

weight in kg divided by height in m2

• BMI between 20 and 25 = healthy
• clinical terms a BMI of 25-30 = overweight
• > 30 = obese
• not a direct measure adiposity and does take in to account increased muscle mass

Question 24

what % body fat is considered obese in men and women

Answer 24

% body fat – obesity defined as >25% in men and >35% in women

Question 25

Explain the central role of glucose in carbohydrate metabolism

Answer 25

- Carbs absorbed as monosaccharides - glucose, galactose, fructose - Monosaccharides undergo enzymatic hepatic interconversion to glucose - large amounts of glucose phosphatase in liver cells - this converts glucose-6-phosphate to glucose - glucose is final common pathway for transport of carbs to tissue cells - glucose high molecular weight so needs facilitated diffusion - glucose transporters - from high to low conc

Question 26

Show how insulin secretion is regulated

Answer 26

insulin secretion turned off by reduced circulating glucose levels amino acids: - mainly arginine and lysine - stimulate insulin secretion - promotes efficient protein metabolism gastrointestinal hormones: - eg gastrin CCK, GIP and GLP-1 - promote secretion - as an anticipatory response Autonomic nervous system: - secretion reduced by sympathetic and increased by parasympathetic

Question 27

describe the metabolic actions of insulin

Answer 27

in adipose tissue: - increase glucose uptake - increase lipogenesis - decrease lipolysis in striated muscle: -

Question 28

describe the effects of insulin on glucose metabolism

Answer 28

Insulin increases facilitated diffusion of glucose Insulin promotes hepatic glucose metabolism: - increase in insulin: > increase in glucokinase - increase glucose uptake > increase glycogen synthetase - increase glycogen storage - decrease in insulin: > increased activity of liver phosphorylase - increased glycogen breakdown > increase activity of phosphatase - increased glucose release

Question 29

describe the effects of insulin on glucose metabolism

Answer 29

Insulin increases facilitated diffusion of glucose Insulin promotes hepatic glucose metabolism: - increase in insulin: > increase in glucokinase - increase glucose uptake > increase glycogen synthetase - increase glycogen storage - decrease in insulin: > increased activity of liver phosphorylase - increased glycogen breakdown > increase activity of phosphatase - increased glucose release Insulin does not influence glucose metabolism in the brain: - Brain cells freely permeable to glucose and utilise glucose as major energy substrate

Question 30

describe glucagon and its action

Answer 30

Produced by pancreatic a-cells in islets of Langerhans Secretion mainly stimulated by decrease in blood glucose Counter-regulatory to the metabolic actions of insulin it promotes hepatic glucose release: - promotes glycogenolysis and gluconeogenesis potent activation via cascade amplification

Question 31

how is glucagon secretion regulated

Answer 31

secretion stimulated by: - decrease blood glucose - increase circulating amino acids - exercise secretion inhibited by: - somatostatin - this has a general suppressive action on metabolism - extends period over which nutrients may be utilised

Question 32

describe how hormones other than glucagon regulate carb metabolism

Answer 32

adrenaline/moradrenaline: - α-adrenergic activation - increase glycogenolysis - increase blood glucose - β-adrenergic activation - increase lipolysis by adipose tissue - more free fatty acids cortisol: - stimulation go hepatic gluconeogenesis - mobilisation of extra hepatic AAs - decrease in glucose uptake in muscle and adipose tissue - increase lipolysis by adipose tissue growth hormone: - increase hepatic gluconeogenesis - increased lipolysis and fattu acid utilisation - decrease tissue uptake of glucose - increased protein synthesis they all protect against hypoglycaemia

Question 33

what is the difference between type 1 and type 2 diabetes

Answer 33

Type 1 Diabetes (~10 % of cases): - insulin-dependent - b-cell dysfunction - viral infection, autoimmune, hereditary - juvenile onset typically ~14 years Type 2 Diabetes (~90 % of cases): - non-insulin dependent - insulin resistance - obesity-related - adult onset typically >30 years

Question 34

name some adverse effects of hyperglycaemia

Answer 34

- tiredness - frequent urination - sudden weight loss - wounds that won't heal - always hungry - blurry vision - numb or time;ing hands or feet - always thirsty

Question 35

describe glycosuria

Answer 35

Normally all filtered glucose reabsorbed in proximal tubule via SGLT1/2 cotransporters and GLUT2 transporters - resulting in return of glucose to circulation - if renal threshold go approx 10mmol/L is reached then the proximal tubule is overwhelmed and excess glucose is excreted in the urine - gliflozins are a drug that decrease renal glucose reabsorption and therefore decrease blood glucose

Question 36

describe glucotoxicity

Answer 36

more glucose = more reactive oxygen speicies - reacts with or alters proteins e.g. advanced glycation end-products (AGE), glycated haemoglobin (HbA1c) - aberrant cellular messaging - chronic inflammation - b-cell dysfunction - endothelial dysfunction - TISSUE DAMAGE

Question 37

describe the consequences of the switch to fat metabolism in uncontrolled diabetes

Answer 37

- increased hormone-sensitive lipase (inhibited by insulin) causes increased lipolysis - this means more free fatty acids taken up bu the liver - this leads to B-oxidation to form ketone bodies (acetoacetate, β-hydroxybutyrate) both of these are acidic - decrease in blood pH and causes metabolic acidosis or diabetic ketoacidosis - build up of H ions compete for binding sites on proteins with potassium (K+) - this means potassium is displaced and leads to hyperkalaemia

Question 38

describe the effect on body protein in uncontrolled diabetes

Answer 38

less insulin means an increased utilisation of protein and fat for energy - this leads to a depletion of body protein therefore untreated diabetes can lead to: - rapid weight loss - asthenia (lack of energy) - polyphagia (increased appetite) - severe tissue wasting

Question 39

describe the diagnosis of diabetes mellitus

Answer 39

Urinary glucose: If blood glucose > ~10 mmol/L, glucose as > renal capacity for reabsorption Fasting blood glucose and plasma insulin: - Normal blood glucose: 3.4-6.2 mmol/L - Normal plasma insulin: ~10 mU/mL (if doing this you can tell T1 vs T2) Glucose tolerance test: Delayed decreased of blood glucose after oral bolus - either decreased insulin or decreased insulin sensitivity Ketoacidosis: decreased insulin signalling - more FFAs - β-oxidation - acetoacetate - acetone

Question 40

Explain the role of amino acids in protein metabolism

Answer 40

Proteins largely absorbed as amino acids via 2o active transport Only small quantities absorbed at any one time as slow digestion Circulating amino acids are taken up by cells within 5-10 minutes Low circulating concentrations; high protein turnover between cells/tissues Amino acids actively reabsorbed in proximal tubules - normal conditions = no amino acid in urine - if protein in tubules exceeds amount then well start seeing protein in the urine amino acids can be converted into a wide variety of proteins with diff functions

Question 41

describe the storage of amino acids

Answer 41

Free amino acids cannot be stored need to be converted to peptides, poly peptides and then intracellular proteins - circulating amino acids usually v low - due to reverse equilibrium od proteins - amino acids stored in form of intracellular proteins - if needed there broken down by enzymes and go into the blood - maintains low levels of circulating AAs but also means there's a constant availability most is stored in the liver but also in kidney and intestinal mucosa cell has limit to amount of protein stored excess amino acids used immediately for energy to converted to fat/glycogen

Question 42

describe transamination

Answer 42

synthesis of non-essential AAs from essential AAs Depends on formation of appropriate α-keto acids which act as precursors Transamination – amino group transferred from amino acid to form α-keto acid

Question 43

describe the use of proteins as a source of energy

Answer 43

Limit to the amount of protein that can be stored by each cell Excess amino acids immediately degraded by liver starting with deamination due to activation of aminotransferases Refers to removal of amino groups from amino acids, occurs by transamination involving reverse process to that related to synthesis of amino acids - deamination is essentially the reverse of transamination

Question 44

describe energetic utilisation of deaminated amino acids

Answer 44

Gluconeogenesis – some products of amino acid deamination (eg. α-ketoglutarate) can enter TCA cycle and produce glucose Ketogenesis forming acetyl CoA or acetoacetyl CoA which enters TCA cycle OR forms ketones

Question 45

describe briefly how urea is formed by the liver

Answer 45

Ammonia released during deamination highly toxic - readily ionises to NH4+ - converted to urea which may then be excreted by the kidneys Urea contains two NH2 groups - one from NH4+ (carbamoyl phosphate) - one from aspartate

Question 46

Outline the hormonal control of protein metabolism

Answer 46

Growth hormone: - Promotes synthesis of cellular proteins - promotes AA membrane transport and RNA transcription/translation Insulin: - Promotes cellular uptake of amino acids, inhibits protein catabolism - increases RNA transcription/translation, inhibits gluconeogenesis - Lack of insulin - increased plasma AAs - energy/gluconeogenesis - muscle wasting Testosterone: - Growth hormone - continual muscle growth - Testosterone - transient muscle growth Oestrogen: - minor muscle growth but insignificant versus testosterone Thyroxine: - increased cell metabolism - activation of anabolic/catabolic protein pathways - less CHO/fat - increased protein degradation, adequate CHO/fat - increased protein synthesis Glucocorticoids: - increase protein breakdown, increase circulating AAs, increase hepatic and plasma proteins - increase gluconeogenesis

Question 47

describe two in born errors of amino acid metabolism

Answer 47

Enzyme defects in the urea cycle Deficiencies in enzymes involved in metabolism of AAs

Question 48

Indicate how nitrogen balance is measured and conditions which may lead to positive or negative nitrogen balance

Answer 48

NITROGEN RELEASED DURING PROTEIN METABOLISM = NITROGEN EXCRETION N-intake > N-loss = +ve N-balance (anabolic state) N-intake < N-loss = -ve N-balance (catabolic state) Measurement: - Estimated by measuring dietary protein intake and urinary nitrogen over 24 h

Question 49

List the types of lipids and their physiological importance Outline the pathway of lipids from ingestion to utilisation in the tissues Describe the types of lipoproteins and understand the differences between them Understand the key factors in the regulation of blood lipid quantity Understand what is dyslipidaemia and why it is a health risk

Answer 49

.

Question 50

List the types of lipids and their physiological importance

Answer 50

1) Triacylglycerol/Triglyceride/neutral fat: - carbon that's part of the carboxylate group at the start of a fatty acid is the alpha - carbon at the end of the fatty acid - part of a methyl group - is called an omega - saturated - only contains single c-c bonds - meat and dairy - unsaturated - contains at lest one c=c bond - mono contains only one double bond - mono is the healthiest fatty acid for you - poly saturated are less healthy than mono but still better than saturated fatty acids - carboxylate group at one end and methyl group bath the other 2. Membrane lipids: - Phospholipids - 2 fatty acids bound to glycerol - Sphingolipids - one fatty acid tail bound to sphingosine

Question 51

List the types of lipids and their physiological importance

Answer 51

1) Triacylglycerol/Triglyceride/neutral fat: - carbon that's part of the carboxylate group at the start of a fatty acid is the alpha - carbon at the end of the fatty acid - part of a methyl group - is called an omega - saturated - only contains single c-c bonds - meat and dairy - unsaturated - contains at lest one c=c bond - mono contains only one double bond - mono is the healthiest fatty acid for you - poly saturated are less healthy than mono but still better than saturated fatty acids - carboxylate group at one end and methyl group bath the other 2. Membrane lipids: - Phospholipids - 2 fatty acids bound to glycerol - Sphingolipids - one fatty acid tail bound to sphingosine cholesterol: - Precursor for synthesis – acetyl co A - no fatty acids in cholesterol molecules - made up instead of parts of fatty acids so has similar properties - steroid nucleus - 4 carbon hydrogen ring structures - in the membrane - maintain fluidity of the membrane - consumed in diet - negative feedback to inhibit own synthesis - cholesterol is esterized - cholesterol esters are its most efficient transport form

Question 52

name some sources of fatty acids

Answer 52

- dietary fatty acids - adipose tissue - endogenously synthesised fatty acids

Question 53

Outline the pathway of lipids from ingestion to utilisation in the tissues

Answer 53

- emulsified by bile - degradation by lipases - absorption and conversion into triacylglycerols - incorporation into chylomicrons

Question 54

what are lipoproteins

Answer 54

lipoproteins: - Molecular complexes that consist of lipids and proteins. They function as transport vehicles for lipids in blood plasma. - Lipoproteins deliver the lipid components (cholesterol and triglyceride etc.) to various tissues for utilization. - Differ in the ratio of protein to lipids, & in the particular apolipoproteins & lipids that they contain - Vary in size & density - as density increases size decreases - as triglycerides are removed from a lipoprotein the density increases

Question 55

what are the functions of apolipoproteins

Answer 55

- Structural component of lipoproteins - Enable transport of lipids - Interact with cell surface receptors - Activate/inhibit enzymes involved in lipoprotein metabolism

Question 56

describe the size, major core lipids, origin and mechanism of catabolism of chylomicrons

Answer 56

see lipid metabolism lecture slide 13 size: up to 1 um ``` major core lipids: dietary triglycerides (TGs) ``` origin: intestine mechanism of catabolism: hydrolysis by LPL in tissues

Question 57

describe the size, major core lipids, origin and mechanism of catabolism of chylomicron remnants

Answer 57

see lipid metabolism lecture slide 13 size: 30-50nm Major core lipids: dietary cholesteryl esters (ChEs) origin: chylomicrons mechanism of catabolism: receptor-mediated endocytosis in liver

Question 58

describe the size, major core lipids, origin and mechanism of catabolism of very low density lipoproteins (VLDL)

Answer 58

see lipid metabolism lecture slide 13 size: 40-100nm Major core lipids: endogenous TGs origin: liver mechanism of catabolism: hydrolysis by LPL in tissues

Question 59

describe the size, major core lipids, origin and mechanism of catabolism of intermetiede density lipoproteins (IDL)

Answer 59

see lipid metabolism lecture slide 13 size: 25-35 nm Major core lipids: endogenous TGs and ChEs origin: VLDL mechanism of catabolism: ~50% receptor-mediated endocytosis in liver; ~50% conversion to LDL

Question 60

describe the size, major core lipids, origin and mechanism of catabolism of Low density lipoproteins (LDL)

Answer 60

see lipid metabolism lecture slide 13 size: 18-28 nm Major core lipids: endogenous ChEs origin: IDL mechanism of catabolism: receptor-mediated endocytosis in liver or tissues

Question 61

describe the size, major core lipids, origin and mechanism of catabolism of high density lipoproteins (HDL)

Answer 61

see lipid metabolism lecture slide 13 size: 5-10 nm Major core lipids: endogenous ChEs origin: intestine, liver mechanism of catabolism: receptor-mediated endocytosis in liver

Question 62

describe the exogenous lipid pathway

Answer 62

see lipid metabolism lecture slides 15-17 Removal of chylomicrons from the blood - Plasma triacylglycerol and cholesterol transport chylomicrons bind dietary triacyglycerols and cholesterol in the intestines they are then transported in the blood in the bloodstream chylomicrons bind to endothelium of capillaries of skeletal muscle and adipose tissue enzyme lipoprotein lipase hydrolyses the triacylglycerols and free fatty acids are released into the tissues what remains is a chylomicron remnant - containing mostly cholesterol - returns from the capillaries chylomicron remnant makes its way to the liver and is taken up by liver by LDL receptors and dietary cholesterol is delivered bile acids and cholesterol are delivered from the liver to the intestines

Question 63

describe the endogenous lipid pathway

Answer 63

see lipid metabolism lecture slides 18-21 manufacture of lipids within the body itself and how those lipids are transported to peripheral tissues VLDL are synthesised in the liver and they deliver endogenous triglycerides and cholesterol to the tissues VLDL delipidated in capillaries by lipoprotein lipase - releases free fatty acids - taken up by cells of muscle and adipose tissue glycerol backbone delivered to liver or kidney cells - to be converted to dihydroxyacetone phosphate dilapidated VLDL emerge from capillaries as intermediated density liporoteins (IDL) after degradation to IDL or LDL, about half are taken up by the liver via receptor-mediated endocytosis tissues other than the liver take up cholesterol from LDL via LDL receptors cholesterol removed from cell surface membranes by HDL - this cholesterol delivered to liver

Question 64

describe reverse cholesterol transport

Answer 64

cholesterol removed from cell surface membranes by HDL - this cholesterol delivered to liver - process still poorly understood

Question 65

describe how blood lipid levels are regulated

Answer 65

regulated by hormones see lipid metabolism lecture slide 25 Insulin – promotion of fat synthesis and storage ``` promote mobilisation of fatty acids and depletion of fat reserves by promoting hormone-sensitive lipase: Stress hormones: - Adrenaline and noradrenaline - glucocorticoids (cortisol) - growth hormone ``` Cause mobilisation of fatty acids and depletion of fat reserves by accelerating metabolic processes: - thyroid hormone

Question 66

describe the use of triglycerides for energy

Answer 66

- Fatty acids enter the mitochondria through carnitine cycle - Undergo b-oxidation - Eventually acetyl-CoA is formed - Glycerol is phosphorylated into glycerol-3-phosphate - Enters the glycolytic pathway - Eventually acetyl-CoA is formed Almost all cells (exception: brain tissue and red blood cells) can use fatty acids for energy

Question 67

what is dyslipidemia what are its primary and secondary causes

Answer 67

``` Higher or lower than normal concentration of lipoproteins in the plasma specifically: ↑ Total Cholesterol (TC) ↑ LDL ↑ TG ↓ HDL ``` Causes: Primary: - genetic disorders Secondary: - diabetes - nephrotic syndrome - hypothyroidism - drug induced - hypertension

Question 68

what are the main sites of calcium absorption, excretion and storage in the body

Answer 68

absorption: small intestine excretion: kidneys storage: bones

Question 69

what are the normal plasma calcium levels

Answer 69

Normal plasma calcium levels are 2.35-2.55 mmol/L two types: diffusible and non-diffusible protein bound within diffusible: ionised (free calcium) and bound to anions within non-diffusible: bound to albumin and bound to globulin

Question 70

what is the effect of pH on protein bound and free calcium

Answer 70

As pH decreases, H+ displaces Ca2+ from binding sites and the amount of iCa2+ increases. Conversely, as the blood pH increases, albumin and the globulins become more negatively charged and bind more calcium, causing the amount of iCa2+ circulating to decrease.

Question 71

what are some of the physiological functions of Calcium

Answer 71

see calcium intro lecture slide 7 - Bones and teeth - Glycogen metabolism - Protein secretion - Plasma membrane integrity - Coagulation

Question 72

what is the action of parathyroid hormone (PTH) on bone kidney and intestine also what are its regulators

Answer 72

Bone: - Short-term: rapid exchange from bone pool to ECF - Long-term: resorption (osteoclasts) Kidney: - reabsorption of Ca2+ - excretion of PO43- - formation of 1,25-dihydroxycholecalciferol Intestine: - Ca2+ absorption Regulators: - Low calcium (Ca2+) - High phosphate (PO43-)

Question 73

describe the action of vitamin D on the intestine kidneys and bone what are its regulators

Answer 73

Actions - Intestine: enhances Ca2+ absorption (increases Ca2+ transport proteins – calbindin-D proteins) - Kidneys: facilitates Ca2+ absorption - Bone: increases calcification & mineralisation (essential for normal osteoblast differentiation & function) Regulators of active form: - PTH - Low PO43-

Question 74

what are the causes of Rickets & Osteomalacia

Answer 74

Osteomalacia - vit D deficiency in adults Rickets - vit D deficiency in children - Lack of dietary vitamin D &/or sunlight (UV) - Malabsorption of fats - Failure to form calcitriol (active vitamin D)– can be due to chronic renal failure

Question 75

who are at risk of vitamin D deficiency

Answer 75

elderly and Those from minority ethnic groups with dark skin such as those of African, African-Caribbean and South Asian origin, because they require more sun exposure to make as much vitamin D

Question 76

what is the regulator for calcitonin and what are its actions on bone and kidneys

Answer 76

Regulator: - High Ca2+ Actions - overall lowers blood calcium - Bone: inhibits resorption - Kidneys: increases Ca2+ excretion

Question 77

what hormones other than calcitonin, vitamin D and PTH act on bone

Answer 77

GH, IGFs: - Promotes positive Ca2+ balance - Excess - gigantism Thyroid hormone: - Essential for normal bone maturation in utero - Excess - osteoporosis Glucocorticoids: - Small amounts essential for normal bone development - Excess – osteoporosis Oestrogen & Testosterone: - Increase bone formation Prolactin: - increased calcium absorption

Question 78

what are the normal levels of calcium and the abnormal levels

Answer 78

Normal calcium ranges from 2.35-2.55 mmol/L Abnormal calcium levels >3.5 mmol/L or < 1.9 mmol/L

Question 79

what is hypocalcaemia, what are its causes and what are the clinical signs

Answer 79

decrease in serum calcium levels Causes: - Hypoparathyroidism - most caused by removal or accidental injury to parathyroid glands during surgery - Pseudohypoparathyroidism - post receptor resistance to parathyroid hormone - target cells resistant - Vitamin D deficiency - vit D needed for calcium absorption Clinical signs: - Hallmark is neuromuscular excitability followed by tetany - because calcium usually stabilises the RMP - can reach threshold more easily - involuntary skeletal muscle contraction which can be fatal

Question 80

what is chvostek's sign, what is a positive response and what does this show

Answer 80

elicitation - tapping on the face at a point just anterior to the ear and just below the zygomatic bone positive response - twitching of the ipsilateral facial muscles, suggestive of neuromuscular excitability caused by hypocalcemia

Question 81

what is trousseau's sign, what is a positive response and what does this show

Answer 81

elicitation - inflating a sphygmomanometer cuff above systolic blood pressure for several minutes positive response - muscular contraction including flexion of the wrist and metacarpophalangeal joints, hyperextension of the fingers, and flexion of the thumb on the palm, suggestive of neuromuscular excitability caused by hypocalcemia

Question 82

what is hyperparathyroidism what are its causes and what are the clinical signs

Answer 82

increased serum calcium Causes: - Primary hyperparathyroidism - problem within parathyroid glands themselves - Secondary hyperparathyroidism - the stimulus is low Ca2+ - Tertiary hyperparathyroidism - after long standing secondary hyperparathyroidism Clinical signs: - ‘Bones’: Bone pain - ‘Stones’: Kidney stones - ‘Groans’: GI disruption e.g. abdominal pain, peptic ulcer, lack of appetite, constipation - ‘Moans’: CNS disturbance - depression of nerves, muscle weakness, lethargy, cardiac conduction abnormalities