An adequate diet is one which contains sufficient fat & CHO to satisfy the body’s energy
requirements, and which provides the minimal amount of protein, vitamins, minerals and
water to prevent deficiency. To maintain our body weight we must stay in energy balance.
The essential components of the diet are:
1) FAT: Required as energy source and for absorption of fat soluble vitamins.
Essential FA are not synthesized in body and must come from diet.
2) CHO: Major energy source. Brain needs a constant supply of glucose which can be
synthesized from non CHO stores (gluconeogenesis) if not adequate in diet.
3) PROTEIN: Essential as a around 35 g/day is lost which must be compensated for
in diet. Essential AA can not be synthesized in body and must be in diet
4) DIETRY FIBRE: Non digestable plant material (e.g. cellulose) is necessary for
normal bowel functioning.
5) VITAMINS & MINERALS: Are essential in diet and deficiency in one or more can
lead to clinical abnormalities.
6) WATER: 50-60% of body weight is water and we must constantly be drinking to
maintain fluid balance and prevent dehydration.
Body weight:
There is a lot of evidence to suggest that both excessive body weight and being
underweight are associated with an early death, so maintaining our desirable weight is
important for good health. A simple and commonly used way to estimate desirable body
weight is to derive the Body Mass Index where the BMI = weight (kg) / height (m2).
Desirable ranges:
Severely Obese:

20-25 (men) and 19-24 (women)
26-30 (men) and 25-30 (women)
30-40 (men & women)

Excess body fat is associated with increased risk of hypertension, heart disease, stroke,
type II diabetes, certain cancers and osteoarthiritis so overweight individuals should be
encouraged to lose weight through sensible diet and exercise. However, for longer term
weight loss, long-term changes in food choices, eating behavior and lifestyle changes are
Malnutrition is any condition caused by an in-balance between what an individual eats and
what that individual requires to maintain health. This may result from eating too little
(under-nutrition) or too much (over-nutrition). Malabsorption conditions (e.g. Coeliac
disease and Crohn’s disease) are caused to digest/absorb ingested nutrients.
Anorexia nervosa is a psychological illness, most common in female adolescents, in
which the patients starve themselves or use other techniques to induce weight loss. They
are motivated by a false perception that there bodies are fat / fear becoming fat.

an enzyme which catalyses addition of OH groups onto Proline molecules. CLINICAL IMPORTANCE: Vitamin and Mineral deficiencies. Overweight/obesity are chronic conditions characterised by excess body fat and are most often defined on basis of BMI.Bulimia nervosa refers to episodes of uncontrolled eating followed by attempts to avoid fattening affects of binges (e.g. VIT K: Is required for clotting cascade & deficiency can lead to coagulation defects (req for correct functioning Prot C which inhibits PAI-1 &  Allows fibrinolysis to take place) ASCORBIC ACID (VIT C): Is required for correct functioning of Proline Hydroxylase. Serum albumin always low. lethargic and anorexic with generalised oedema. FOLIC ACID: Is required for nucleic acid synthesis and supplements before conception decrease the occurrence of neural tube defects (e.g. They are caused by eating more food than needed. IRON: Is required for oxygen transport in haemoglobin and deficiency can lead to anaemia. Vit C deficiency leads to synthesis of weakened collagen and therefore “poor wound healing and bleeding gums”. Abdomen is distended due to hepatomegaly and/or ascites. VIT D: Is involved in calcium absorption and deficiency can lead to Osteomalacia in adults and Rickets in children. Marasmus is the type most commonly seen in children under age of 5 where the child looks emaciated with obvious signs of muscle wasting and loss of body fat although there is no oedema. Protein-energy malnutrition covers a spectrum of clinical conditions seen in starving adults and children. the surplus of which is converted to fat and stored around the body. Child is apathetic. . Kwashiorkor occurs typically in a young child displaced from breast feeding by a new baby and fed a diet with a very low protein content. self induced vommitting). allowing the tight triple helicle “procollagen” molecules to form. Spina Bifida) in pregnancy.

It is the concentration of free T4 which determines metabolic affects Hypothalamus Major physiological actions of T3 & T4 T3 & T4 stimulate an increase metabolic rate and activity in many tissues – their affects are generally catabolic.B: TRH = Thyrotrophin-Releasing Hormone . There are two main cell types found in thyroid gland: follicular cells and parafollicular cells. It is normally only palpable when it is enlarged (goitre) and two nerves lie in close proximity to the gland – the recurrent laryngeal and the external branch of the superior laryngeal. The follicular cells are arranged in numerous functional units called follicles while the parafollicular cells are found in CT. they cause an increase in BMR. Capilleries Colloid Epihelial cells A “Follicle” (Extra-cellular storage site of T3/T4) Hormones produced in thyroid gland The gland produces 3 hormones: Follicular cells 1) Thyroxine (T4) 2) Tri-idothyronine (T3) 3) Calcitonin – Parathyroid cells Synthesis thyroid hormones TSH. These nerves are in danger of being damaged in thyroid surgery and must be avoided as they supply the larynx and are involved in speech. stimulates production of thyroxine (T4). However. Transport of thyroid hormones in blood T3 & T4 are hydrophobic and are transported in blood bound to proteins such as thyronine binding globulin (TBG) and albumin. TSH is the hormone which binds to receptors on the surface of follicular cells and stimulates all aspects of the synthesis and secretion of T3 & T4.THYROID FUNCTION Location thyroid gland The gland is in the neck and lies in front of larynx and upper trachea. heat production and increased oxygen consumption. Structure of thyroid gland The gland consists of two lateral lobes. Iodine and tyrosine are combined to form either T3 or T4. response of target tissues to T3/T4 is slow and may take days/weeks to manifest themselves. joined by a central isthmus. released from Ant Pit. These are stored extra-cellularly bound to thyroglobulin (a specific binding prot) in colloid. It is attached by CT to larynx and therefore moves with swallowing. Secretion thyroid hormones Thyroglobulin is taken into epithelial cells where proteolytic cleavage of the throglobulin occurs to release T3 & T4 which then difuse into circulation via cappileries. - TRH ↓ Ant Pit TSH ↓ Thyroid T3/T4 ↓ Blood Free T3/T4 ↓ TISSUES N.

If the deficiency is not corrected within a few weeks of birth irreversible damage occurs. It is an autoimmune disease in which antibodies are produced which stimulate the TSH receptors on follicular cells resulting in increased production and release of T3 & T4.  Skin dry and flaky with Alopecia (hair loss)  Voice is deep and husky  Females – menorrhagia & infertile. Signs & symptoms in adults: (general slowing down)  Cold intolerance and reduced BMR  Weight gain  Tiredness and lethargy  Bradycardia  Neuromuscular weakness. all newborns have their thyroid function assessed soon after birth. especially for development of the nervous system (including myelination of nerves and hyperplasia of cortical neurons). CLINICAL IMPORTANCE – Cretinism In the absence of thyroid hormones from birth to puberty. Thyroid disease: Hypothyroidism The most common form of hypothyroidism is Hasimoto’s disease affecting aprox 1% of population mostly women. increased oxygen consumption & increased BMR  Weight loss  Physical and mental hyperactivity  Tachycardia  Intestinal hypermobility  Skeletal and cardiac myopathy leading to tiredness. inside the tissues. the child’s nervous system does develop correctly and the infant remains mentally and physically retarded. Constipation Treatment:  Patients generally treated with oral thyroxine. In UK. Thyroid disease: Hyperthyroidism The most common form of hyperthyroidism is Grave’s disease affecting aprox 1% population mostly women. T4 can be converted to T3. However.T3/T4 are required for normal growth & development. . weakness and breathlessness. It is an autoimmune disease which results in either the destruction of thyroid follicles or the production of an antibody that blocks TSH receptor on follicle cells preventing them from responding to TSH. Mechanism of action of T3 & t4 T3 & T4 cross the plasma membrane of target cells and interact with receptors in nucleus and possibly mitochondria. muscle cramps and cerebellar ataxia. Signs & symptoms in adults: (general speeding up)  Heat intolerance.  Osteoporosis due to increased bone turnover and preferential resorption Treatment:  Patients may be treated with Carbamizole – a drug which inhibits the incorporation of iodine into thyroglobulin. Receptors have higher affinity for T3 than T4.

CLINICAL EXAMINATION OF THYROID GLAND Get patient to sit forward in chair. 2-3 months of thyroid hormone are stored within the follicles and this delays the onset of symptoms in deficiency diseases. depression and anaemia. is goitre regular.  Hoarse voice  Face puffy facial appearance. A physical examination of the thyroid gland should also be performed.  Perform “Lid-Lag test” – Patient follows clinicians finger from above eye to below eye. Inspection:  Inspect gland from front. ensuring adequate exposure (neck and upper chest). especially apparent in Achilles tendon reflex. you should rule out the possibilities of the signs and symptoms being due to chronic fatigue. . Signs  Delayed reflexes. get patient to swallow on command to establish if goitre moves or not. Also: If hypothyroidism is suspected. Palpation:  Explain what you will do!  Stand right and slightly behind. Get patient to hold breath. Then swallow on command to assess if thyroid moves  Palpate carotids  Palpate regional lymph nodes Percussion:  Assess reterosternal expansion by percussing over manubrium and upper sternum Auscultation:  Listen to each lobe for Bruits. newly noted cold intolerance.diffuse. smooth goitre with audible bruit (due to ↑ vascularisation).CLINICAL ASSESMENT OF THYROID STATUS When assessing for possible diseases of thyroid there are a number of specialised tests that can be done following a good history. symmetrical etc. CLINICAL SIGNIFICANCE: The thyroid gland is the only endocrine gland to store its hormone in an extrcellular compartment. HYPOTHYROIDISM Symptoms  Suspect hypothyroidism in patients complaining of unexplained lethargy. Signs  Test for tremor by placing a sheet of paper on outstretched fingers  Facies: Staring appearance (caused by retraction of upper eyelid). palpate lobes with both hands – gently! Reasure!  Assess texture. HYPERTHYROIDISM Symptoms  The patient will generally be warm and sweaty with tachycardia.  From front. In hyperthyroidism the upper eyelid lags behind eye mvmt.  Examine goitre . heat intolerance and weight loss. weight gain. palpitations. constipation and pain in hands suggestive of CTS.

Cortisol. Mechanism Action: Cortisol can cross the Plasma membrane where it binds to receptors in cytoplasm. CRF is released in response to physical (pain. Aldosterone. Androgens & Adrenaline. an outer cortex and an inner medulla. Aprox 10% is free and biologically active. The blood supply to the gland is unusual as it has a portal system that directly connects a capillary bed in hypothalamus with a capillary bed in Pituitary gland. CORTISOL Cortisol is a member of the steroid family and is therefore produced from cholesterol. Hormones of Anterior Pituitary:  TSH produced in the Thyrotrophs  ACTH produced in the Corticotrophs  GROWTH HORMONE produced in the Somatotrophs  LH & FSH produced in Gonadotrophs.PITUITARY & ADRENAL GLANDS The Pituitary Gland The Pituitary gland is located at the base of the brain suspended from the hypothalamus by a stalk.g. chemical (hypoglycaemia) and emotional (psychological) stressors. The Anterior Pituitary develops from nonneural secretory epithelial and has no direct conection with hypothalamus (has portal blood supply). The gland has two lobes that arise from two histiologically different tissues and as such function as two separate endocrine glands. Hormones of Posterior Pituitary:  ADH  OXYTOCIN The Adrenal glands The adrenal glands are a pair of multifunctional endocrine glands that cap the upper ploes of the kidneys and lie against the diaphragm. Transport Cortisol: Cortisol is a steroid. The secretion of cortisol is controlled by ACTH (Adrenocorticotrophic Hormone) released from Ant Pit which in turn is controlled by Corticotrophin releasing factor (CRF) released from hypothalamus. temp). The Adrenal glands produce the following hormones: Mineralocorticoids e. Cortisol is therefore slow acting. so in plasma it must be transported bound to transport protein (transcortin). Cortisol has a negative feedback affect on both hypothalamus and pituitary. Glucocorticoids – e. Hormone/receptor complex then enters nucleus and interacts with specific regions of DNA to change the rate of transcription. Control of Adreno-Corticol function Physical Stress - Chemical Stress Hypothalamus CRF ↓ Anterior Pituitary ACTH ↓ Adrenal Cortex CORTISOL ↓ Blood ↓ TISSUES Emotional Stress .g. The glands consist of two regions. as well as an arterial blood supply from the superior and inferior hypophyseal arteries arising from the internal carotid artery. The Posterior Pituitary develops from neuroectoderm of the primitive brain tissue and a direct neural conection exists between the hypothalamus and Post Pit.  PROLACTIN produced in Lactotrophs.

aldosterone) and would produce a complex situation that may present as a medical emergency (Addisonian crisis) or as a chronic debilitating disorder (Addison’s disease):  Insidiuos onset with initial non-specific symptoms of tiredness. vomiting and even coma.  FAT: ↑ Lipolysis in adipose tissue. nausea. Clinical affects of reduced cortisol secretion:  Reduced secretion caused by autoimmune destruction of adrenal gland. Must be treated immediately to prevent death. weight loss and dizziness. extreme muscular weakness.B: high levels of cortisol = ↑ lipogenesis in adipose tissue DISORDERS OF ADRENOCORTICOL FUNCTION Addison’s disease – Hypoactivity of adrenal cortex: Decreased activity of the adrenal cortex (Addison’s disease) can be due to:  Autoimmune diseases causing destruction of adrenal cortex resulting in reduced glucocoticoids and mineralocorticoids. ↑ proteolysis = Causes use prot as fuel!  CHO: ↑ hepatic gluconeogenesis and glycogenesis. especially on fasting (due to lack cortisol). ↓ Prot synthesis.Actions of Cortisol on target cells: Cortisol is an important component of the stress response and it has a number of impt affects on metabolism. The major metabolic affects are in the starved and stressed states where it affects the availability of all major metabolic substrates by increasing proteolysis. Clinical affects of excess cortisol secretion:  Increased muscle proteolysis & hepatic gluconeogenesis that may lead to hyperglycaemia with associated polyuria and polydipsia (steroid diabetes)  ↑ Muscle proteolysis leading to muscle wasting &  thin arms + legs. upper arms & thighs reflecting catabolic affects on prot structures in skin leading to easy bruising. extreme dehydration.g. neck and face producing characteristic body shape &moon shaped face  Purple striae on abdomen. Due to either pituitary adenoma or ectopic secretion ACTH.  Disorders in hypothalamus/pituitary that lead to reduced ACTH which only causes reduced glucocorticoids.  Extreme muscular weakness and dehydration  Decreased blood pressure due to sodium and fluid depletion (aldosterone) causing postural hypertension. vague Abdominal pain. Cushings syndrome: Hyperactivity of adrenal coertex Increased secretion of glucocorticoids (Cushings syndrome) can be due to:  Adenoma: A tumour of adrenal cortex (adenoma) can cause increased secretion of glucocorticoids  Cushings disease: Is a disorder which causes increased secretion of ACTH. . would also involve the loss of mineralocorticoids (e.  These affects may be exasherbated by stress/trauma and may lead to a clinical emergency (Addisonian crisis) where the patient has fever.  PROT: ↓ AA uptake.  ↑ Lipogenesis in adipose tissue leading to deposition of fat in abdomen. lipolysis and gluconeogenesis. N.  Hypoglycaemic episodes.

g. Mineralocoticoid affects of excess cortisol (cortisol can bind mineralocorticoid receptors!) may produce hypertension due to sodium & fluid retention. May be back pain and collapse ribs due to Osteoporosis caused by disturbances in calcium metabolism. N. CLINICAL IMPORTANCE: Clinical tests of adrenocorticol function  Measurement of plasma cortisol & ACTH  The 24hr measurement of urinary excretion of cortisol and its degration products. cataracts in eye. . Galactitol accumulation in eye can lead to Glaucoma. The digestion of lactose occurs in the duodenum and jejunum by the action of enzyme Lactase.B: Dexamethasone is a potent synthetic steroid that. Galactosaemia is a relatively rare clinical condition whereby affected individuals can not utilise dietary galactose due to a deficiency in one of the 3 main regulatory enzymes of galactose metabolism (galactokinase. where dietary galactose is converted toglucose 6-phosphate. DISORDERS OF CHO METABOLISM: GALACTOSEMIA & LACTOSE INTOLERANCE GALACTOSEMIA  Galactose metabolism takes place mainly in the liver.B: Many of these signs and symptoms occur in patients receiving longterm treatment with glucocoticoids for varois chronic inflammatory conditions.  Clinically: May present with diarrhoea. Dexamethasone suppression of plasma cortisol by >50% is characteristic of Cushings syndrome while suppression does not normally occur in adrenal tumours or ectopic ACTH production.  The commonest and most severe enzymatic defect is due to GAL-1-PUT deficiency. The intramuscular injection of Synacthen (a synthetic analogue of ACTH) would normally increase plasma cortisol by >200nmol/l. Amenorrhoea due to suppression of pituitary-ovarian axis by cortisol. giving rise to vommitting accompanied by hypoglycaemia. A bacterial infection can thrive off sugar leading to gastroenteritis. when given orally would normally suppress (by feedback inhibition) the secretion of CRF and thus ACTH and cortisol.  Clinically: The accumulation of galactose in tissues will result in galactose being reduced to galactitol with subsequent depletion of NADPH and cross-linking of proteins e. vomiting. dehydration and frothy/watery stools. anti-inflamatory & anti-allergic affects of cortisol leading to increased susceptibility to bacterial infection and acne. Undigested sugar in GI tract causes re-absorption water and diarrhoea developing. N. which usually manifests itself in the neonatal period or early infancy. LACTOSE INTOLERANCE  Lactose is a dietary dissacheride composed of glucose-galactose.  Dynamic function tests: Dexamethasone suppression tests and ACTH stimulation tests. gaactose 1-phosphate uridyltransferase (GAL-1-PUT) etc).  Low activity of Lactase is associated with a reduced ability to digest the lactose present in milk products and may produce clinical condition of lactose intolerance.     Immunosuppression. A normal response usually excludes Addison’s disease.

↑ glycogenesis. There is two types of glandular tissue.THE PANCREAS The pancreas is approximately 15cm long and lies behind the stomach. insulin is stored in vesicles where it undergoes post-translational modification to cleave a connecting peptide (cpeptide) to activate it into mature insulin. skeletal muscle and adipose tissue) to bring about the following affects:  ↑ glucose transport into cells. Following its synthesis and targeting to the golgi of the  cells. ↓ ketogenesis (liver) & ↑Lipoprotein lipase activity in cap. It is a gland which contains both Endocrine and Exocrine components. ↑ lipogenesis (liver/adipose).g. Insulin interacts with surface receptors on target cells (the main target tissues being liver. Glandular tissue is epithelial cells that have been specialised for secretion. and chymotrypsinogen  Endocrine secretions include:  Glucagon (alpha cells)  Insulin (beta cells) Insulin Insulin is a polypeptide hormone which is made in the  cells of the endocrine pancreas.  ↓ Lipolysis. Exocrine glands secrete their products into ducts while Endocrine glands secrete directly into the circulation. defined on the basis of the method of secretion. The Exocrine component of the Pancreas consists of closely packed secretary acini which secrete into a highly branched duct system. Levels of C-peptide are therefore an excellent way of measuring endogenous insulin secretion in patients on Insulin. Mechanism of Action of Insulin: The action of insulin is mainly anabolic relating to its major function of clearing absorbed nutrients from blood following a meal. beds of tissues such as adipose tissue. Glucagon Glucagon is a single polypeptide hormone which is synthesized and secreted from the cells of the islets of langerhans cells in the pancreas in response to low/drop in blood glucose concentration. GI tract hormones and ACH stimulation where mature insulin and C-peptide are released in equimolar amounts. AA. ↓glycogenolysis and ↓gluconeogenesis. FA). insulin and somatostatin respectively. beta and gamma cells which secrete glucagons. The Endocrine cells of the pancreas consist of clumps of secretary cells (about 3000/per clump) called islets of langerhans which are composed of alpha. activates glycogen phosphorylase to cause ↑ glycogenolysis.  Exocrine secretions from acini include:  Pancreatic Amylase  Pancreatic lipase  The pro-enzymes trypsinogen. Glucagon’s actions are mainly catabolic as it is an anti Insulin which works to cause a . Insulin is released by exocytosis at plasma membrane in response to increased metabolites (glucose. It acts on cell surface receptors at target cells to activate/deactivate key enzymes e. Its affects are mainly rapid but has long term affect of increasing DNA replication.  ↑ AA uptake & protein synthesis (liver/musc/adipose) and ↓ proteolysis.

1 mmol/L OR 2) A Fasting plasma glucose conc above 7 mmol/L OR 3) A plasma glucose conc above 11. Affects on individual:  High blood glucose will lead to appearance of glucose in urine. In the absence of symptoms.  WEIGHT LOSS: caused by increased lipolysis and proteolysis as glucose is absent from tissues. virus) to produce an auto-immune response that attacks & destroys beta-cells ( Type I = autoimmune destruction -cells) Presentation: Classic picture is of a lean young person with a recent history of viral infection. ↑glygogenolysis.Prostration. KETONE BODIES: Are only made in liver! Production of them depends upon an availability of FA + plasma insulin/glucagons ratio to be low ( Never made when glucose availability high).g.generalised increase in fuel availability (e. dehydration. They are water soluble (easily transported in blood) and are an impt fuel molecule as they can be used by all tissues cont mitchondria inc CNS. abdominal pain. insulin resistance or both.  Features of Ketoacidosis (a metabolic acidosis associated with H+ from ketones): . Type I Cause: A genetic predisposition interacts with an environmental trigger (e. who presents with a triad of symptoms:  POLYURIA: excess urine produced due to the osmotic affects of high glucose in urine (due to high blood glucose!)  POLYDIPSIA: increased thirst due to excess water loss and osmotic effects of glucose on thirst centres. then diagnosis must not be made on the basis of a single glucose test but should have at least one other glucose test result within the diabetic range on a different day. nausea. There are two types of diabetes. Clinically: When present in high conc in plasma can cause ketoacidosis as they are relatively strong oranic acids. DIABETES MELLITUS Diabetes Mellitus is a group of chronic metabolic disorders characterised by chronic hyperglycaemia due to insulin deficiency.g. gluconeogenesis & ketogenesis in liver & ↑lipolysis in adipose tissue).1 mmol/L 2 hrs after an OGTT. Diagnosis: Is made on the presence of symptoms and either: 1) A Random venous fasting plasma glucose conc above 11. This can be predicted by smell of acetone on breath (nailvarnish remover) and ketones in urine.  This presentation must be dealt with urgently to prevent life-threatening crisis of ketoacidosis. CLINICAL IMPORTANCE: Never make a diagnosis of diabetes on the basis of glucose in urine or a stick reading of a finger prick test! . vomiting.

diabetic neuropathy. during hyperglycaemia. Persistant hyperglycaemia is also associated with increased non-enzymatic glycosylation of plasma proteins which leads to disturbed function. Macrovascular complications: Increase risk stroke. Thus the % of HbA1c is a good indicator of the effectiveness of blood glucose control over last 2-3 months (as RBC’s stay in circulation aprox 120 days). no symptoms + 2 readings in diabetic range (on diff.g. Treatment: Type II DM can sometimes be managed by diet or “oral hyperglycaemic drugs” that increase insulin release from remaining beta-cells. However. appropriate dietary management & regular exercise are important. . Type II DM may have been present long before diagnosis Diagnosis: Same as Type I: – Symptoms + 1 reading from tests in diabetic range OR. This glucose is then combined with NADPH and H+ (catalysed by aldose reductase) to produce sorbitol and NADP+. Metabolic consequences of persistant hyperglycaemia The uptake of glucose at peripheral nerves. MI and poor circ to peripherys (especially feet) Microvascular complications: Diabetic eye disease (esp. Type I managed for rest of patients life with self injected Insulin. Therefore. persistant infections (particularly genetalia & feet). For example. Presentation: Patients may present with classical triad of symptoms but likely to present with lack energy. Prevention: Diet and exercise have been shown to ↓ risk of dev Type II DM. Patients must be educated to take insulin at times to mimic the normal release of insulin from islets of langerhans (e. but is determined by extra-cellular glucose concentration. HbA1c is usually about 4-6% but can be +10% in poorly controlled diabetics.Treatment: No cure. diabetic kidney disease.retinopathy). diabetic feet.meals). cataracts). but lifestyle factors contribute to Type II DM (e. Days). Thus. intracellular glucose concentration in these tissues rises. hyperglycaemia depletes NADPH leading to increased disulphide bridge formation on intracellular proteins (e. appropriate dietary management and regular exercise.g. Type II Cause: The slow progressive loss of -cells may have some genetic predisposition. over eating/lack exc contribute insulin resistance). slow healing (of minor skin damge) and visual problems. Glycosylation of Lipoproteins affects their function and may be involved in dev of atherosclerosis. Glycosylated haemoglobin (HbA1c): Glucose in blood reacts with terminal valine of HB to produce glycosylated haemoglobin.g. eye and kidney does not require insulin.

Treatment: Special diet to reduce phenylalanine & increase tyrosine (life-long intervention that will require dietary tyrosine). The stability of the lipoprotein depends upon the ratio of core to surface lipids. FA is transported bound non-covalently to albumin 1) Chylomicrons: Transport dietary triacylglycerols from s. Stabilising lipoproteins: As TAG are removed by Lipoprotein lipase. PKU will inhibit brain development (as tyrosine required for thyroxine which is needed for normal neural development) an can cause metabolic acidosis (phenylactate ect).intestine to adipose tissue 2) VLDL: Transport synthesized triacyyglycerols from liver to adipose tissue.PHENYLKETONURIA (PKU): All babies in the UK are screened for PKU by a blood test (heel prick) at 6-14 days. Structure of Lipoproteins: All lipoproteins found in man are spherical structures that consist of a surface coat (shell) and a hydrophobic core. Insulin increases activity and synthesis of Lipoprotein Lipase and hence diabetics will be less receptive to liporoteins. The surface coat contains the phospholipids. in PKU the enzyme PHENYLALANINE HYDROXYLASE is defective resulting in severely reduced tyrosine production and increased phenylpyruvate. 4) HDL: Transport excess tissue cholesterol from tissues to liver (for disposal). the enzyme Lecithin: Cholesterol Acyltransferase (LCAT) converts cholesterol (surface) to . The FA enters cell while glycerol is taken to liver. Phenylalanine hydroxylase PHENYLALANINE O-HYDROXYPHENYL METABOLITES TYROSINE PHEYLPYRUVATE Thyroid hormones Catecholamines Melanin PHENYL-LACTATE PHENYLACETATE Classically. cholesterol) in blood.It is found attached to the inner surface of capillaries at tissues such as adipose tissue & muscle. the enzyme Lipoprotein Lipase is responsible for removing the core TAG from lipoproteins . If untreated. the lipoprotein becomes more unstable as ratio of surface to core lipids increases. PKU is an alteration in the the metabolism of Phenylalanine. However. increasing concentration lipoproteins and hence lipids (inc. LIPID TRANSPORT Lipids are mostly hydrophobic (except ketones) and must therefore be transported with proteins as Lipoproteins. cholesterol and apoproteins while the hydrophobic core contains TG and cholesterol esters. Removal core lipids: Once at the tissues. 3) LDL: Transport synthesized cholesterol from liver to tissues. This may contribute to development of atherosclerosis in diabetics. Liporotein Lipase hydrolyses the TAG to release FA and glycerol.

Removal core lipids destabilises lipoproteins but enzyme Lecithin cholesterol Acyltransferase (LCAT) converts cholesterol (surface) to cholesterol esters (core) and thus stabilises molecule. the plasma cholesterol +/OR plasma TAG is raised. Summary: Lipids transported in liporoteins. When investigating get patient to have a blood test after a 12 hr fast and conduct the following tests: 1) Plasma glucose concentration (to check fasting sample and/or diabetes) 2) Total serum cholesterol (reference range below 5. synthesise receptors that recognise specifically Apoprotein B (the protein component of LDL). FA enter cell while glycerol goes to liver. In Familial Hypercholesterolaemia: An absence (homozygotes). Cells that require cholesterol. 6 types of hyperlipoproteinaemias can be identified.0 mM) 4) Plasma Lipoprotein separation by gel electrophoresis (to examine lipoprotein profiles) Based on these tests. CLINICAL IMPORTANCE: HYPERPLIPOPROTEINAEMIAS Hyperliporoteinaemia is any condition in which. 2) Drug therapy: Statins – are a group of drugs that may be useful in lowering cholesterol levels by reducing the synthesis of cholesterol in the tissues. 3) Drug therapy: Bile salt sequestants – lower plasma cholesterol by increasing its disposal from the body. lipoprotein lipase is enzyme which removes TAG from core of lipoprotein molecule by hydrolysing TAG into FA & glycerol.9 mM) 3) Serum Triacylglycerol (reference range 0. Treatment: 1) Diet and lifestyle modifications – use these first! Aim is to reduce / eliminate cholesterol from diet. Binding of Apoprotein B to LDL receptor causes internalisation of both receptor and ligand (LDL) to endosomes (CURL) where acidic environment (of endosomes) causes dissacociation of LDL and receptor. . after a 12 hr fast.cholesterol esters (core lipid) and thus stabilises the lipoprotein. Whole process takes around 10 minutes from start to finish. The LDL then goes to lysosome where it is hydrolysed to release cholesterol while receptors are recycled back to mem.5-2. HYPERCHOLESTEROLAEMIA Cholesterol enters target cells by the process of receptor-mediated endocytosis. or deficiency (heterozygotes) of functional LDL receptors leads to elevated LDL and cholesterol in plasma. reduce TAG (especially those containing saturated FA) and increase exc. Homozygous individuals may develop atherosclerosis in early thirties. leading to early onset of atherosclerosis. Deficiency in the enzyme results in unstable lipoproteins and increases risk developing atherosclerosis. Raised Liporoteins are important clinically as they are associated with CAD. Insulin increases activity & synthesis Lipoprot lipase and so diabetics are less responsive to liporoteins. TYPE IIa is raised LDL only and is associated with severe CAD. At tissues. Deficiency in LCAT will increase development atherosclerosis.

“my dad died at 38 from a heart attack”.History is important: As affected individuals will probably have a family history of heart disesase / early deaths from heart disease e. .g. There are two major clinical signs: 1) CORNEAL ARCUS. 2) TENDON XANTHELASMA Treatment: Is diet & lifestyle modifications with statins (Hmg CO-A reductase inhibitors).