FULL UNIT 8 REVISION Flashcards
what is bilirubin
- Yellow bile pigment produced through haemolysis
types of bilirubin
conjugated and unconjugated
unconjugated bilirubin
insoluble in water, only travel in the bloodstream if bound to albumin
conjugated bilirubin
soluble in water, can be directly excreted
stages of bilirubin metabolism
creation
conjugation
excretion
creation stages of bilirubin metabolism
- Haem is broken down into iron and biliverdin catalysed by haem oxygenase
- Iron gets recycled
- Biliverdin is reduced to created unconjugated bilirubin
conjugation stages of bilirubin metabolism
- Unconjugated bilirubin will bind to albumin to transport to the lvier
- Glucuronyl transferase adds glucuronic acid to unconjugated bilirubin
- Conjugated bilirubin can be excreted into the duodenum in bile
excretion stages of bilirubin metabolism
- Colonic bacteria deconjugate bilirubin into urobilinogen
- Further oxidised to make sterocobilin
- Excreted in faeces
- Minority of urobilinogen is reabsorbed into the bloodstream in enterohepatic circulation, oxidised in the kidneys to urobilin and excreted in the urine
digestion in the mouth
- Mechanical :mastication
- Reduces size of ingested particles
- Mixes food with saliva, exposing to digestive enzymes
- Increases surface area of the ingested material - Chemical
- Alpha amylase, ptyalin: cleaves internal alpha 1,4-glycosidic bonds in starch, maltos, maltotriose and alpha limit dextrins produced
- Linguinal lipase: hydrolysis of dietary lipids, 3 fatty acids and 1 glycerol
stomach acid secretion
- Gastrin and acetylcholine activate phospholipase C
- PLC catalyses the formation of inositol triphosphate IP3
- IP3 causes release of intracellular Ca2+ and activates calmodulin kinase
- Calmodulin kinase phosphorylates variety of proteins leading to H+ secretion
- ECL cells have cholecystokinin receptors for gastrin
- Gastrin stimulates ECL cells to release histamine
- Histamine activates adenylate cyclase to form cyclic AMP
- Protein kinase A phosphorylates variety of proteins leading to H+ secretion
H+ secretion stomach
- H+ pumped actively into the lumen in exchange for K+ through ATPase
- Cl- enters cells across basolateral membrane in exchange for HCO3-
protein digestion in the stomach
proteins stimulate the G cells to secrete gastrin into the blood
- Gastrin stimulates the ECL cells in the lamina propria to release histamine
- Histamine stimulates acid secreting parietal cells
- Gastrin stimulates parietal cells to release HCl and intrinsic factor and the chief cells to release pepsinogen
- Pepsinogen converted to pepsin which cleaves the protein
- Negative feedback: low antral pH causes D cells to release somatostatin to inhibit G cells to prevent over secretion of acid
digestion of fats in the stomach
- Gastric lipase produced by chief cells in the fundus
- Stimulated by neurohormonal stimuli e.g. gastrin and cholinergic mechanisms
- Inhibited by cholecystokinin and glucagon like peptide GLP-1
digestion of carbohydrates in the stomach
- Salivary amylase is inactivated due to low pH
- Chemical activity is low
- Mechanical breakdown is ongoing
- Strong peristaltic contractions of the stomach mix into chyme via propulsion and retropulsion
duodenum inhibiting gastric emptying
- CCK increases distensibility of the orad stomach
- Acid inhibits motility and emptying
- Secretin and GIP inhibit
carbohydrate digestion in the small intestine
- Pancreatic amylase released following stimulus of secretin and CCK
- Starch digested into maltose, maltotriose and alpha limit dextrins
- Oligosaccharides and disaccharides digested at the brush border by lactase, sucrase, isomaltase and maltase
fat digestion in the small intestine
- Bile acts as an emulsifier to increase the surface area
- Lipase converts lipids to fatty acids and glycerides
- Bile salts envelop the fatty acids and monoglycerides to micelles and at the brush border they will diffuse out of the micelles to absorptive cells
protein digestion in the small intestine
- Proteases: trypsin and chymotrypsin
- Brush border enzymes: peptidases hydrolyse dipeptides and amino acids
absorption of monosaccharides across the intestinal wall
- SGLT1 for glucose uptake
- Energised by the electorchemical Na+ gradient
- Maintained by the extrusion of Na+ across by the Na-K pump by secondary active transport
- Facilitated diffusion mediated by GLUT5 for fructose absorption to the enterocyte
- Facilitated diffusion by GLUT2 across basolateral membrane to interstitial space
glycaemic index
cells in the small intestine
metabolism
catabolism
anabolism
catabolism
breakdown of complex molecules to release energy, glucose and adrenaline
anabolism
use of energy to construct molecules, insulin
what does insulin promote in the liver
- Glycogen synthesis
- Glucose metabolism
- Adipogenesis
what does insulin inhibit
- Glycogen breakdown
- Gluconeogenesis
what does glucagon/adrenaline promote
- Glycogen breakdown
- Gluconeogenesis
glycogenesis
Glycogen synthesis: glycogenesis
- Glucose enters the liver via GLUT2
- Converted by glucokinase to G-6-P
- Insulin then converts G-6-P to glycogen
glycolysis
- Glucose enters liver via GLUT2 receptors
- Converted by glucokinase to G-6-P
- Insulin promotes conversion of G-6-P to pyruvate
- Insulin promotes PDH to convert pyruvate into acetyl-CoA
- Which either enters the citric acid cycle to form CO2
- Or lipogenesis occurs and fatty acids are formed
glycogenolysis
Glycogen breakdown: glycogenolysis
- Glucagon and adrenaline break down stored glycogen
- To glucose-6-phosphate
- Glucose-6-phosphatase then converts glucose-6-phosphatase to glucose
- Which leaves the liver via GLUT2 receptors
- This process is inhibited by insulin
gluconeogenesis
Gluconeogenesis: glucose formation
- Glucagon and adrenaline act on pyruvate
- Form glucose-6-phosphate
- Acted on by glucose-6-phosphatase
- To form glucose
- Leaves the liver via GLUT2 receptors
- Inhibited by insulin
glucagon and adrenaline lead to what
upreg of adenylate cyclase, converts ATP to cAMP, activates cAMP dependent protein kinase, phosphorylates glycogen synthase and glycogen phosphorylase
what does phosphorylation lead to
deactivation of glycogen synthase and activation of glycogen phosphorylase
glucose metabolism after overnight fast
- Low insulin to glucagon ratio so anabolism off and catabolism on
- Gluconeogenesis occurs via alanine, lactate and glycerol
- Leaves the liver as glucose and transported to the brain and the muscles
- High glucagon promotes gluconeogenesis
- Glucose is in short supply so preserved for use by the brain
glucose metabolism in the fed state
- High insulin to glucagon ratio so anabolism on and catabolism off
- Brain continues to use glucose but other tissues switch to using glucose for metabolism and storage following uptake from small intestine and release of insulin from the pancreas
- Muscle: glucose metabolism and glycogen storage
- Adipose: glucose taken up and stored as fat
- Liver: glycogen storage promoted and gluconeogenesis suppressed
potential uses for fat metabolism in the liver
Potential uses for fat metabolism in the liver:
1. Storage in adipose tissue transported by VLDL
2. Energy production: B oxidation to acetyl CoA to the citric acid cycle then electrons down ETC to oxidative phosphorylation
3. Ketone bodies: gluconeogenesis byproduct
4. Cholesterol: steroid hormones, bile, fat soluble vitamins
Or stored in the liver then released as:
1. Plasma lipoproteins: VLDL and HDL
2. Free fatty acids: alternative energy supply for mitochondria
fat metabolism in the liver, no insulin
- Without insulin fatty acids entry to the mitochondria and ketone body synthesis are unrestricted
- Allows the body to function in the absence of glucose
- But can lead to Diabetic KetoAcidosis ini type 1 diabetes
lipogenesis
Lipogenesis: formation of fatty acids
- Glucose enters and binds with acetyl co enzyme A
- Addition of insulin and Co2 will form malonyl-CoA
- Forms fatty acids
- Either stored or exit via fatty acid transporters
how is triacylglycerol formed
- Fatty acids bind to co-enzyme A to form fatty acyl Co-A
- Bind with insulin and glycerol 3-P to form triacylglycerol
how are ketone bodies formed
- Fatty acids bind to coA
- Froms faty acyl-CoA
- Addition of glucagon will cause breakdown by beta oxidation
- To form CO2 and ketone bodies
- Ketone bodies will leave the liver
fatty acid metabolism in the fasting state
- Low insulin to glucagon ratio so lipolysis is promoted
- Triacylglycerol broken down into NEFA which is a FFA used as energy by the muscle, liver and kidney and converted to ketone bodies, some back to TAG
- Glycerol is also a product and used by the liver for TAG production, glycolysis and gluconeogenesis
- Anabolism off and catabolism on
fatty acid metabolism in the fed state
- Insulin activates lipoprotein lipase
- Fat absorbed from the small intestine is packaged in chylomicrons
- Transported to the lymphatics
- Activation of lipoprotein lipase in adipose tissue and muscle releases NEFA
- Taken up and stored as TAG
HDL
: good cholesterol
- Tightly bound to cholesterol
- Doesn’t detach onto arterial walls
- May pick up additional cholesterol to reduce size of deposits
LDL
: bad cholesterol
- Deposits cholesterol onto walls of arteries
- Oxidizes and damages lining of arteries
uses of amino acids in the liver
- Synthesis of liver/plasma proteins (albumin) / clotting proteins (fibrinogen and prothrombin) except immunoglobulins
- Released via blood for tissue protein synthesis
- Conversion to nucleotides, hormones
- Catabolism via urea cycle
- Pyruvate and acetyl coA for intermediate steps in gluconeogenesis and glycogen storage, energy production, fatty acid synthesis
- Alanine form the muscle is converted into pyruvate and used for energy in the citric acid cycle or gluconeogenesis
10 amino acids made in the liver
alanine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine and tyrosine
10 essential amino acids in the diet
arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine
transamination
- Conversion of one amino acid to another
deamination
removal of an amino group from a molecule, occurs in the hepatocytes
triglyceride synthesis
- Glycerol and 3 fatty acids
- Stored for future use as triacylglycerols primarily in adipocytes
adipose in whoel body metabolism
- Fatty acids transported from the liver to the adipose in VLDL
- Glycerol generated from glucose
- Fatty acids and glycerol combined to form TAG
- TAG broken down to fatty acids and glycerol by HSL
- Hormone sensitive lipase activated by glucagon and adrenaline
- Fatty acids transported into the blood and attached to albumin
- Glycerol recycled into TAG or transferred to liver for gluconeogenesis
role of muscle in whole body metabolism
- Fasted state: uses fatty acids and ketone bodies for energy
- Fed state: glucose metabolism, converts to acetylCoA via pyruvate
- Pyruvate to lactate anaerobically to generate muscle energy
fat cell development
- Fibroblast like precursor cells receive hormone signals
- Trigger differentiation to adipocytes
- Cells alter gene expression pattern
- Accumulate lipid droplets
- Lipids accumulate and merge together to form mature fat cell (triglyceride droplet and nucleus)
- Mature fat cells cant divide
- But early stages are reversible
white adipose tissue
- Hypertrophy and hyperplasia during long term positive energy balance
- Produces steroid hormones, proteins of energy metabolism, blood clotting and complement pathway, cytokines, peptide hormones including leptin
- “Fat” fat cells: promote insulin resistance
- “Thin” fat cells: regulate metabolic interplay and promote glucose uptake
adipocyte changes in obesity
modest weight gain increase cell size
at maximum size
futher weight gain causes the recruit of pre-adipocytes to differentiate
weight loss the cell number doesnt decrease
weight gain cell size increases
carbohydrate metabolism of adipocyte in the fed state
- Increased glucose transport
- Increased glycolysis
- Increased hexose monophosphate pathway HMP: metabolism of glucose produces NADPH for fat synthesis
fat metabolism in the adipocyte in the fed state q
- Increased fatty acid synthesis
- Decreased triglyceride hydrolysis
adipocyte in the fasting state carbohydrate metabolism
- Glucose transport and metabolism depressed due to low insulin, decreased fatty acid and triglyceride synthesis
fat metabolism in adipocyte fasting state
- Increased triglyceride hydrolysis
- Increased fatty acid release
- Decreased fatty acid uptake
leptin
- Produced in adipose tissue in proportion to adipose mass
- Leptin treatment reduces food intake, increases energy expenditure and reverses obesity in ob/ob mice
- Leptin only works in individuals who are obese due to leptin deficiency
- Most obese people have leptin resistance
adiponectin
liver glucose production
muscle glucose oxidation
resistin
promtoes insulin resistance
tnf alpha
impairs glucose signalling
glucose trasnprt
il-6
increases lipolysis
glucose uptake
fatty acids
impairs insulin production in the pancreas
sensitivity
thrifty genes
- Permit more efficient food utilisation and fat deposition
- In times of abundance
- Better survival in times of subsequent famine
- In current times: energy rich, calorie heavy diet, reduced energy expenditure, leads to obesity and type 2 diabetes
role of the CNS in weight regulation
- Lateral hypothalamus: lesion in this area, animals become anorectic and lose weight
- Ventromedial hypothalamus: lesion in this area animals overeat, become obese
hunger
increased ghrelin from stomach
fed state hormones
glucose
insulin
stored energy hormones
leptin and RBP4 production in proportion to fat content, RBP4 reduces tissue insulin sensitivity, adiponectin antagonises RBP4 but falls in obesity
NPY
increase food intake and decrease physical activity
AgRP
increase appetite, decrease metabolism
POMC
regulates alpha melanocyte stimulating hormone which regulates appetite and sexual behaviour
what do appetite signals do
These act on the hypothalamus
Leptin and insulin decrease appetite by inhibitory actions on NPY and AgRP
Signal well-fed state
Ghrelin from empty stomach activates NPY and AgRP
PCT
- Na+ Transport: Na+ is actively transported out of the tubular lumen into the epithelial cells of the PCT through the Na+/K+ ATPase pump located on the basolateral membrane. This creates a concentration gradient for Na+ to passively diffuse into the cells from the lumen.
- K+ Transport: K+ moves passively between the tubular lumen and the epithelial cells through leak channels.
- Glucose Transport: Glucose is reabsorbed through secondary active transport. Na+/glucose symporters on the luminal membrane couple the reabsorption of glucose with the facilitated diffusion of Na+ into the cells.
loop of henle
- Thin Descending Limb: No active transport of Na+, K+, or glucose occurs in this segment. Water is reabsorbed passively.
- Thick Ascending Limb: Na+ is actively transported out of the tubular lumen into the epithelial cells through Na+/K+/2Cl- symporters. K+ can leave the cells through K+ channels. Glucose is not reabsorbed in this segment.
DCT
- Na+ Transport: Na+ is reabsorbed in exchange for K+ secretion. Na+ enters the epithelial cells through Na+/Cl- symporters or Na+ channels. Na+/K+ ATPase pump on the basolateral membrane maintains low intracellular Na+ concentration.
- K+ Transport: K+ is actively secreted into the tubular lumen through K+ channels located on the luminal membrane. This secretion is regulated by aldosterone.
- Glucose Transport: Glucose reabsorption is minimal in the DCT.
collecting duct
- Principal Cells: Na+ is reabsorbed through epithelial Na+ channels (ENaC) in exchange for K+ secretion. This process is regulated by aldosterone. Glucose is not reabsorbed.
- Intercalated Cells: Involved in K+ and H+ transport rather than Na+ and glucose.
glomerular filtration rate
rate roughly 125ml per minute and is the amount of blood filtered through the glomeruli each minute
calculating renal blood floq
: pressure in the renal artery- pressure in the renal vein all divided by the resistance in the renal arterioles
hormones involved in increasing blood flow
adrenaline
angiotensin 2
adrenaline increasing blood flow
adrenal gland in response to sympathetic stimulation
binds to alpha 1 adrenergic receptors on afferent and efferent arterioles
causes contraction of smooth muscle cells
leading to constriction
low renal blood flow
angiotensin 2 increasing blood flow
final product in RAAS system, travels through blood, binds to recpetors on afferent and efferent arterioles and causes constriction, leads to a low renal blood flow.
To maintain GFR: efferent are more receptive to angiotensin 2 than the afferent, low angiotensin 2 only the efferent will constrict, more blood remains in the glomerulus, GFR preserved. In high levels then decreased renal blood flow and GFR
decreasing blood flow
- Atrial natriuretic peptide: from atria of the heart
- Brain natriuretic peptide: from the ventricles of the heart
- Secreted when there is an increased cardiac workload and the walls of the atria and ventricles are stretched, bind to natriuretic peptide recpetos on smooth muscles
- Leads to the dilatin of afferent and constriction of efferent to increase the renal blood flow
- Prostaglandins: E2 and I2 produced in the kidney with sympathetic stimulation, causes the dilation of the afferent and constriction of the efferent to increase the renal blood flow even in fight or flight
- Dopamine: synthesised in brain and kidneys. Brain is neurotransmitter. Binds to dopaminergic receptors on smooth muscle cells and constricts the capillaries in skin and muscle nut dilates in the heart and kidney. Both afferent and efferent dilated. Low dopamine concentrations will increase renal blood flow
autoregulation of blood flow
local mechanisms in the kidney which keep renal blood flow and GFR constant over range of systemic blood pressure, kidney adjusts own arteriolar resistance
mechanisms of kidney autoregulation
myogenic
tubular glomerular
myogenic autoregulaiton
reflex of smooth muscle cells to contract when stretched, more stretch is more likely to contract, leads to constriction of afferent and efferent
tubular glomerular mechanism
DCT and glomerulus, DCT loops to be close to afferent= juxtaglomerular apparatus, macula densa cehmorecpetor, detect when GFR increases due to the concentration of sodiu, and chloride ions
Blood pressure rises, renal blood flow rises, GFr rises, more fluid, more nacl reaching macula densa, macula densa release adenosine, diffuses to juxtagomerular cells, increases arteriolar resistance, decreases GFR
what is RAAS
- Renin angiotensin aldosterone system
- Activated when blood volume and blood pressure drops
- What is the point? To restore blood volume and blood pressure
describe the RAAS system
- Renin:
- Drop in blood volume/ blood pressure is stimulus
- In afferent arteriole there are juxtaglomerular cells/ granular cells
- Release renin (enzyme)
- Cells are baroreceptors, and notice the drop in blood pressure in the afferent arteriole
- Another way it is released: filtrate moves slowly if the blood volume is lower, so more sodium can be filtered out, less sodium in the DCT, macula densa cells are chemorepeotrs measuring the concentration
- Macula cells in dct in close proximity and connected by connective tissue to the granular cells so renin is secreted
- Another way: increased sympathetic nervous system innervation - Renin leaves the kidney
- Liver has stored angiotensinogen
- Angiotensinogen is released into the bloodstream, renin converts angiotensinogen to angiotensin 1
- Angiotensin 1 is slight vasoconstrictor but not really clinically relevant
- Angiotensin 1 to the lungs where high conentraiotns of angiotensin converting enzyme ACE
- Converts angiotensin 1 to angiotensin 2
- Angiotensin 2 is a generalised vasoconstrictor, increasing blood pressure
- Angiotensin 2 consrtricts efferent arteriole, increases GFR, increases sodium in DCT
- Angiotensin 2 to the cortex of the adrenal gland, stimulates aldosterone release
- Aldosterone to the DCT, promoting Na+ and H2O reabsorption, increasing blood volume and blood pressure
- Angiotensin 2 to the hypothalamus, posterior pituitary, releases ADH, water reabsorption in DCT and CD, increases blood volume and blood pressure
alcohol ADH pathway
ADH converts alcohol to acetaldehyde
ALDH oxidises acetaldehyde to acetate
generate hydrogen converting NAD to NADH
promotes fat accumulation
alcohol MEOS pathway
- Chronic excessive alcohol consumption induces the MEOS (mainly in endoplasmic reticulum), increasing its activity.
- The main enzyme involved is CYP2E1.
- When induced, the MEOS pathway can account for 20% of alcohol metabolism.
- This pathway generates harmful reactive oxygen species, increasing oxidative stress and formation of oxygen-free radicals.
chlamydia
chlamydia trachomatis
intracellular bacteria
enter via T3SS
elementary bodies with spore like cells wall for resistance
reticulate bodies
once in the cell will convert into reticulate bodies
replicate exponentially by binary fission
turn back into elementary bodies and leave through lysis or extrusion
chlamydia symptoms
vaginal/penis discharge
burning/itching sensation on urination
pain/ swelling in testicles or stomach
transmitted by bodily fluids, pregnant woman to baby and unprotected sex
syphilis
treponema pallidum
bacterial spirochete
syphillis symptoms
painless sores
rash on palms of hands and feet
flu like
transmitted by unproteted se and pregnant women to baby
gonorrhoea
neisseria gonorrhoea
gram negative diplococci
anaerobic
non motile
gonorrhoea symptoms
discharge
green or yellow
burning sensation
lower abdo pain
transmitted: bodily fluids unprotected and pregnancy
HPV
small non enveloped icosahedral double stranded
genital warts
get the vaccine
differentiation between HSV and HPV
HSV spread by drinks, utensils, towels and lip blams
HSV
large double stranded DNA in a capsid
cant be cleared
trichomoniasis
trichomonas vaginalis parasite
