ENDOCRINE and REPRODUCTIVE PHYSIOLOGY

ENDOCRINE/REPRODUCTIVE PHYSIOLOGY PHY 546 Jill Davis Cleveland Chiropractic College Kansas City 1 Chemical Messaging • Exocrine – Ducted glands – Secretes substances into hollow organs or body surface • Endocrine – Ductless glands – Secrete hormones into bloodstream • Paracrine – Cells secrete substances that affect neighboring cells 2 Chemical Messaging • Autocrine – Secretes substances that affect the cell which secreted the substance • Neural signaling – Neurotransmitters secreted by neurons – Paracrine/autocrine signaling • Neuroendocrine signaling – Hormone secreted into blood by a neuron 3 Endocrinology Basics • Anatomy/histology of each gland • Hormone(s) secreted – Chemical classification – Synthesis • Target tissue(s) – Receptor type and mechanism 4 Endocrinology Basics • Major effects of the hormone • Regulation of secretion – What stimulates secretion – What inhibits secretion • Common pathologies concerning hypersecretion • Common pathologies concerning hyposecretion 5 Hormone classification • Peptides/proteins • Amine Hormones (derived from tyrosine) – Catacholamines – Thyroid hormones • Steroids 6 Peptide/protein Hormones • • • • • • • Structure – peptide (<100 a.a.) protein (>100 a.a.) Solubility – hydrophilic Synthesis – on RER, packaged in Golgi Storage – mostly in secretory granules Secretion – exocytosis of granules Plasma transport – as free hormone Receptor site – cell membrane 7 Catacholamines Structure – tyrosine derivative Solubility – hydrophilic Synthesis – in cytosol Storage – in chromaffin granules Secretion – exocytosis of granules Plasma transport – some free/ some bound to plasma proteins • Receptor site – cell membrane 8 • • • • • • Thyroid Hormones • • • • • • • Structure – iodinated tyrosine Solubility – lipophilic Synthesis – colloid space of thyroid gland Storage – in colloid and cytosol in thyroid cells Secretion – endocytosis from colloid/diffusion Transport – bound to plasma proteins Receptor site – nucleus of target cell 9 Steroids • • • • • • • Structure – cholesterol derivative Solubility – lipophilic Synthesis – various intracellular compartments Storage – none Secretion – diffusion Plasma transport – bound to plasma proteins Receptor site – cytosol or nucleus 10 Overview of Endocrine Glands • Hypothalamus – various releasing and inhibitory hormones (most are peptides) • Anterior Pituitary – TSH, ACTH, Prolactin, FSH, LH (peptides) • Posterior Pituitary – ADH/vasopressin, oxytocin (peptides) • Thyroid – thyroxine and triiodothyronine (amines) • Adrenal Cortex – cortisol, aldosterone (steroids) • Adrenal medulla – norepinephrine/epinephrine (amines) 11 • Pancreas – insulin, glucagon (peptides) Overview of Endocrine Glands Parathyroid – parathyroid hormone (peptide) Testes – testosterone (steroid) Ovaries – estrogens, progesterone (steroids) Placenta – HCG (peptide), others Kidney – Renin, EPO (peptides), 1,25 Dihydroxycholecalciferol (steroid) • Heart – atrial natriuretic peptide • Stomach – gastrin (peptide) • Small intestine - secretin, CCK (peptides) 12 • • • • • Regulatory Mechanisms • Negative feedback • Positive feedback (rarely) • Cyclical patterns of secretion 13 Transport Water soluble hormones (peptides & catacholamines) – dissolved in plasma Lipid soluble hormones (steroids & thyroid hormones) – bound to plasma proteins 14 Clearance • Hormone concentration in blood – Rate of secretion – Clearance rate • • • • • Metabolic destruction Biding to tissues Excretion by liver into bile Excretion by kidneys into urine Bound vs. unbound hormones 15 Terminology • Down regulation – a hormone induced response that produces fewer hormone receptors on the target cell – Desensitization – functional response in target tissue to hormone down regulation 16 Terminology • Up regulation – a hormone induced response that produces more hormone receptors on the target cell. – Sensitization – the functional response in target tissues to hormone up regulation • Antagonism – two hormones having opposite effects on the target tissue – or causes down regulation of another hormone’s receptor. 17 Terminology • Permissiveness – Where one hormone must be present in order for another to be effective • Synergism – Where two hormones produce complementary effects when combined (two hormones upregulate each other) 18 Hormone Receptor Locations • In/on cell surface – Integral to or attached to the cells membrane – Used by peptide/protein and catacholamine hormones • In the cell cytoplasm – Used by steroid hormones • In the cell nucleus – Used by thyroid hormones 19 Basic Actions of Hormonereceptor Binding • Change in membrane permeability – Activation of extracellular receptor – Opening or closing of ion channels – Action can be direct (first messenger) or indirect (activation of second messenger) 20 Basic Actions of Hormonereceptor Binding • Activation of intracellular enzyme – Activation of extracellular receptor – Activation of intracellular second messenger • Activation of genes – Activation of intracellular receptor – Leads to activation of DNA within nucleus, or increased mRNA translation 21 Review of Second Messenger Systems • Second messengers – an intracellular chemical messenger that is activated by the binding of an extracellular chemical messenger (first messenger) to a surface receptor. • G-protein (GTP binding protein) – mediates activation of second messenger enzyme. There are several forms of this protein. • Amplification – successive steps of activation cause multiple second messengers to be formed from binding of one first messenger • Adenylyl Cyclase – cAMP system (fig 74-4) 22 Review of Second Messenger Systems • Phospholipase C – PIP2 IP3 + DAG system (fig 74-5) • Calcium-Calmodulin system 23 Pituitary Gland (Hypophysis) • Location – sella turcica – attached to hypothalamus via pituitary stalk • Anatomy – Anterior lobe (adenohypophysis, pars distalis) – Intermediate lobe (pars intermedia) – Posterior lobe (neurohypophysis, pars nervosa) 24 Anterior Lobe • Histology – Derived from Rathke’s pouch – Acidophilic cells • Somatotrophs – GH • Lactotrophs – prolactin – Basophilic cells • Corticotrophs – ACTH • Thyrotrophs – TSH • Gonadotrophs – FSH, LH 25 Posterior Lobe • Histology – Pituicytes – neuroglial-like cells – Axons of neuroendocrine cells • Expanded axon terminals = Herring bodies • Cell bodies are located in supraoptic and paraventricular nuclei of hypothalamus. • Connected via hypothalamo-hypophyseal tract 26 Intermediate Lobe • Histology – Also derived from Rathke’s pouch – Is a rudimentary structure in humans – Produces some hormones • Melanocyte stimulating hormone (MSH) • Opiates (POMC, endorphins) 27 Hypothalamic Control of Pituitary Secretions • Anterior Pituitary – Neurosecretory cells of the hypothalamus secrete releasing and inhibiting hormones: • • • • • • Thyrotropin-releasing hormone (TRH) Corticotropin-releasing hormone (CRH) Growth hormone releasing hormone (GHRH) Growth hormone inhibiting hormone (GHIH) Gonadotropin-releasing hormone (GnRH) Prolactin inhibitory hormone (PIH) – Hypothalamic-hypophyseal portal system 28 Hypothalamic Control of Pituitary Secretions • Posterior Pituitary – Nerve signals from the hypothalamus terminate in the posterior pituitary gland and control secretion. • Supraoptic nucleus – ADH (vasopressin) primarily • Paraventricular nucleus – oxytocin primarily 29 Pituitary Hormones • Adenohypophysis – – – – Human growth hormone (hGH, somatotropin) Adrenocorticotropin (ACTH) Thyroid-stimulating hormone (TSH) Gonadotropic hormones • Follicle stimulating hormone (FSH) • Luteinizing hormone / (LH) – Prolactin / (PRL) • Neurohypophysis – stores and secretes only – Antidiuretic Hormone (ADH, vasopressin) – Oxytocin 30 Growth Hormone • A.k.a. – somatotropic hormone or somatotropin • Classification – Protein • Synthesis – GH mRNA codes a prehormone, which is cleaved to form GH, stored in secretory vesicles 31 Growth Hormone • Target Tissues – Almost all tissues of the body capable of growing – Some tissues affected differently than others – Secreted in pulses 32 Growth Hormone • Growth effects – increase cell size and/or stimulates mitosis – Stimulates differentiation of bone and muscle cells • Metabolic effects - Protein – Increased rate of protein synthesis in most tissues • Increased amino acid transport into cells • Increased mRNA translation • Increased mRNA transcription – Decreased catabolism of protein 33 Growth Hormone • Metabolic Effects - Fats – Increased mobilization of fatty acids from adipose tissue • Release of fatty acids increase blood concentration • May lead to “ketosis” if excessive – Increased utilization of fatty acids for energy • Enhances conversion of fatty acids to acetyl Co-A 34 Growth Hormone • Metabolic Effects – Carbohydrates – Decreased glucose uptake in skeletal muscle and fat – Increased glucose production in liver – Increased insulin secretion (may be compensatory) – Carbohydrate effects may be due to release of fats – Synergism – GH and insulin are both necessary for growth 35 Growth Hormone • Somatomedin (Insulin-like GF) – GH stimulates its release from liver – Mediates GH’s effect on bone growth 36 Growth Hormone • Regulation of GH secretion – Stimulates secretion: • • • • • • Starvation / protein deficiency Hypoglycemia or low FA in blood Exercise Excitement Trauma First 2 hours of deep sleep 37 Growth hormone • Hormonal Regulation – Growth hormone releasing hormone • • • • Secreted from the hypothalamus (ventromedial nucleus) Stimulates somatotrophs via cAMP pathway Has both long term and short term effects GH - negative feedback loop – Growth hormone inhibitory hormone (somatostatin) • Secreted from the hypothalamus • May be stimulated by GH • Probably less important regulator of GH secretion 38 Growth Hormone • Clinical Correlations – Panhypopituitarism • Decreased secretion of all all adenohypophyseal hormones • Congenital or caused by pituitary destroying tumor, or thrombosis of pituitary gland • Effects – hypothyroidism, adrenal insufficiency, infertility, dwarfism (in children) – Dwarfism • Panhypopituitarism or GH deficiency alone • Can be mutation in gene for somatomedin – Giantism(children, teens) • Growth hormone secreting tumors of pituitary gland – Tall stature, hyperglycemia, – Acromegaly (adult) • Enlargement of especially membranous bones 39 Antidiuretic Hormone (ADH) • A.k.a. – vasopressin • Structure – polypeptide • Produced by neurosecretory cells of the supraoptic nucleus (~66%) and released by posterior pituitary by exocytosis • Target tissues – kidney and arterioles 40 Antidiuretic Hormone (ADH) • Effects on collecting ducts / tubules of the nephron (kidney) – Mechanism – cAMP  phosphorylation of aquaporincontaining vesicles  inserts into tubular membrane  increases H2O permeability  increases H2O reabsorption – Effect – antidiuresis – Reversible • Effects on arterioles – Causes vasoconstriction  increases blood pressure – Effect seen in higher concentrations 41 ADH • Regulation of ADH secretion – Osmotic regulation • osmoreceptors in hypothalamus sense increased electrolyte concentration  increase ADH secretion – Decreased blood volume and arterial pressure • stretch receptors in atria – overfilling inhibits ADH secretion • Baroreceptors in carotid, aortic, pulmonary arteries – too much pressure inhibits ADH 42 Oxytocin • Structure – polypeptide • Produced by neurosecretory cells of the paraventricular nucleus (~66%) and released by posterior pituitary by exocytosis • Target Tissues – uterus and breast 43 Oxytocin • Effect on uterus – Stimulates smooth muscle contraction  important for delivery of babies • Effect on breast – Stimulates myoepithelial cells in mammary alveoli to contract to cause milk “let down” into the ducts – Stimulated by suckling 44 Thyroid Gland • Location - near junction of larynx and trachea • Anatomy - Right and left lobes connected by isthmus • Histology – Follicles – simple cuboidal epithelium lining a colloidfilled lumen (thyroglobulin) – Parafollicular cells (clear cells) – Has an extensive blood supply 45 Thyroid Hormones • Synthesis – Iodide • Absorbed from the GI tract • Iodide trapping – active transport of I- into follicle cells • Transported to lumen of follicle and oxidized by peroxidase / H2O2 to form iodine – Thyroglobulin • Synthesized by RER and Golgi • Is a large glycoprotein containing many tyrosine residues • Iodinase links iodine to tyrosine residues to create MIT, and DIT • 2 DIT are linked together to form thyroxine (T4) • 1 MIT and 1 DIT are linked to form triiodothyronine (T3) 46 Thyroid Hormones • Thyroglobulin is the storage form of T3 and T4 in the thyroid gland • Release of T3 and T4 – Pseudopod extension and pinocytosis – Lysosomal proteinase cleavage of T3, T4, MIT, and DIT off of thyroglobulin – MIT and DIT are deiodinated and recycled – T3 and T4 are released into the blood 47 Thyroid Hormones • Secretion rates – 93% thyroxine (T4) – 7% triiodothyronine (T3) – T3 is most potent, however, T4 slowly becomes deiodinated in the blood to form T3 • Transport – Strongly bound to plasma proteins – Slow release to tissue cells 48 Thyroid Hormones - Functions • Nuclear receptors – Hormone-receptor complex functions as a transcription factor – 100’s of genes are activated therefore 100’s of proteins are synthesized – All responses to thyroid hormones are secondary to this increase 49 Thyroid Hormones - Functions • Increases basal metabolic rate (kcal/m2/hr) – – – – – Increases rate of utilization of foods for energy Increases protein synthesis AND catabolism Increases # and size of mitochondria Increases ion transport Decreases body weight/increases appetite 50 Thyroid Hormone - Functions • Carbohydrate metabolism – – – – – Increases uptake Increases glycolysis Increases gluconeogenesis Increases absorption Increases insulin secretion • Fat metabolism – Increases mobilization and utilization of free fatty acids – Decreases cholesterol, phospholipids and triglycerides (more is secreted in the bile) 51 Thyroid Hormone – Functions • Other systemic effects – Increased CO and Q (blood flow) • Due to increased demand / autoregulation • Increased heat  skin vasodilation • Increased HR and strength of contraction (however too much can weaken heart) – Increased respiration – Increased GI motility 52 Thyroid Hormone - Functions • Other systemic effects - continued – – – – Excitatory to nervous system (reduced sleep) Muscle irritability – tremor Increased endocrine gland secretions Increased growth rate • Important in fetus and infancy • Matures epiphyseal plate 53 Regulation of Thyroid Hormone Secretion • TSH – thyroid stimulating hormone , thyrotropin – From adenohypophysis – Increases T3 and T4 secretion • protolysis of thyroglobulin • iodide pump activity • size of thyroid cells • TSH is in turn controlled by TRH – Thyrotropin releasing hormone – From hypothalamus 54 TRH and TSH Regulation • Exposure to cold – increases TRH and therefore TSH as well • Anxiety and excitement – decreases TRH and TSH • Thyroid hormones – negatively feedback on TSH 55 Hyperthyroidism • Causes – Graves Disease – autoimmune disease – Thyroid adenoma – tumor • Symptoms – – – – – – – Hyper-excitability Intolerance to heat / sweating Weight loss Muscle weakness Inability to sleep Tremors (hands) Exopthalmos 56 Hypothyroidism • Causes – Thyroiditis – autoimmune – Iodide deficiency – others • Symptoms – Opposite to that of hyperthyroidism – Cretinism – infancy/young childhood – decreased mental development – Myxedema – adult – accumulation of fluid – puffy features. 57 Adrenal Gland • Location – at the superior poles of each kidney • Anatomy – Capsule surrounded by adipose – Cortex- secretes the corticosteroids – Medulla – functionally related to the SNS • Histology – Adrenal cortex – Zona glomerulosa – underneath capsule – Zona faciculata – middle layer – Zona reticularis – deep layer near medulla 58 Adrenal Glands - Hormones • Cortex (corticosteroids) – Mineralcorticoids (aldosterone) – Glucocorticoids (cortisol) – Sex steroids (androgens, estrogens) • Medulla – Epinephrine (adrenalin) – Norepinephrine (noradrenalin) 59 Adrenal Cortex • Mineralcorticoids – effect electrolyte balance – Aldosterone (most potent, 90% of total activity) – Desoxycorticosterone (low secretion, low activity) – Secreted by zona glomerulosa 60 Adrenal Cortex • Glucocorticoids – effect macronutrient metabolism – Cortisol (most potent, 95% total activity) – Corticosterone (little activity) – Secreted by zona fasciculata • Sex steroids – DHEA and androstenedione – Precursors to testosterone and estrogens – Secreted by the zona reticulata 61 Adrenal Cortex • Corticosteroid synthesis – Synthesized from cholesterol • De novo synthesis from acetate (small amounts) • LDL in plasma – Cholesterol converted in mitochondria to pregnenolone – Pregnenolone is transported to SER for further steps in the pathway (se fig 77-2) 62 Adrenal Cortex • Corticosteroid Transport – 90-95% cortisol bound to plasma proteins – 60% aldosterone bound to plasma proteins • Metabolism – occurs in the liver – Secreted into bile – Excreted by kidneys 63 Aldosterone • Target Tissues – – – – Kidney (distal tubules and collecting duct) Large intestine epithelium Sweat glands Salivary glands • Effects – Increased reabsorption of sodium coupled with increased excretion of potassium 64 Aldosterone • Mechanism – – – – – Lipid soluble Cytoplasmic receptor protein Diffusion into nucleus Induces gene transcription Increase synthesis of enzymes and membrane transport proteins • Sodium-potassium ATPase –basolateral membranes • Sodium channel protein – luminal membrane 65 Aldosterone • Effects on Kidney DT and CD – – – – Increases Na reabsorption increases K excretion Increases water absorption Increases extracellular fluid volume / increases blood pressure – “aldosterone escape” and pressure natriuresis and diuresis 66 Aldosterone • Effects on Sweat glands and Salivary glands – Increases Na absorption and increases K excretion – Conserves Na loss in saliva and sweat • Effects on Intestinal epithelial cells – Increases Na absorption and increases K excretion – Prevents loss of sodium in stools and therefore water is absorbed 67 Aldosterone • Regulation of Aldosterone Secretion – Stimulation of secretion • Hyperkalemia • Renin-angiotensin system – Inhibition of secretion • Hypernatremia (slightly) – Permissive hormone • ACTH – necessary for aldosterone secretion, but does not control rate of secretion 68 Hypo-secretion of Aldosterone • • • • • • • • Hyperkalemia Hyponatremia (and decreased Cl) Decreased extracellular fluid volume Decreased cardiac output Arrhythmia (heart failure) Hypovolemic (circulatory shock) Death in a few days-weeks Addison’s Disease – autoimmune disease, TB, cancer, also effects glucocorticoids 69 Hyper-secretion of Aldosterone • Primary aldosteronism / Conn’s Syndrome – caused by tumor of ZG cells • Kypokalemia • [NaCl] near normal because of pressure natriuresis • ECF volume increases (reaches max because of pressure diuresis) • Hypertension • Muscle weakness 70 Cortisol • Principle Target Tissues – Liver – Skeletal muscle – Adipose tissue • Mechanism – Similar to aldosterone 71 Cortisol Effects • Acts permissively to facilitate mobilization of fuels – Carbohydrate metabolism • • • • Increases gluconeogenesis and glycogenesis (liver) Increases glucose-6-phosphatase (liver) Decreases sensitivity to insulin Decreases glucose uptake – Protein metabolism • Accelerates protein breakdown, inhibits synthesis (mostly in muscle) • Decreases amino acid uptake • Conversion of protein to glycogen (liver) 72 Cortisol Effects – Fat metabolism • Increases lipolysis (adipose) • Excess causes preferential fat deposition in trunk, face, abdomen 73 Cortisol - Effects • Resists stress – Sources of stress include: trauma, infection, temperature extremes, debilitating disease, etc. – Mobilization of fuels from non-essential tissues makes them available to critical tissues • Anti-inflammatory effects – – – – – Decreases arachidonic acid/inflammatory mediators Stabilizes lysosomes Decreases leukocyte recruitment Decreases phagocytosis Decreases T-cell (and indirectly B-cell) activity 74 Cortisol - Regulation • CRF (corticotropin-releasing factor) – Hypothalamus – Stimulated by physical or emotional stress, hypoglycemia • ACTH (adrenocorticotropic hormone) – From anterior pituitary – Sole regulator of cortisol secretion 75 Cortisol - Regulation • Cortisol – Negative feedback on CRF and ACTH secretion • Circadian Rhythm – Cortisol secretion is higher in morning than in evening 76 Cortisol Hypersecretion • Cushing’s Syndrome/disease – Causes: • • • • • • • • • • • Adenoma of anterior pituitary ( ACTH) Abnormal CRH release from hypothalamus Ectopic ACTH secretion from tumor Adrenal cortex adenoma ( cortisol) “buffalo torso”, thin extremities “moon face” Hyperglycemia Depressed immune function (infections) Abdominal striae ( collagen) Osteoporosis May have some symptoms of hyperaldosteronism 77 – Signs & Symptoms Hypoadrenalism • A.k.a. – Addison’s disease – Mixed – both aldosterone and cortisol are undersecreted – Causes - Atrophy of adrenal cortex (autoimmune, cancer, TB) – Signs & Symptoms •  Mineralcorticoid -  Na reabsorption, hyperkalemia, reduced ECF volume etc. •  Glucocorticoid – hypoglycemia, muscle weakness, mental sluggishness, reduced resistance to stress 78 Adrenal Medulla • • • • Derived from neural crest Is analogous to a sympathetic ganglion Innervated by preganglionic neuron Secretes 80% epinephrine 20% norepinephrine (catacholamines) • Effects same as for neural release, but last longer (released slowly) • Released from chromaffin cells 79 Catacholamines – Target tissues • Most cells of the body (metabolic effects) • Cardiovascular tissue • Glands (pancreas, anterior pituitary) 80 Catacholamine Effects • Epinephrine – – – – – – – – Adrenergic receptor affinity 1=2, 1 = 2 Reduces peripheral resistance (vasodilation Heart rate – mixed effect Increased cardiac muscle contractility Increased lipolysis Increased metabolism (heat production) Increased glycogenolysis and gluconeogenesis (liver) Increased glucagon, decreased insulin, increased ACTH 81 Catacholamine Effects • Norepinephrine – – – – – – – Also is a neurotransmitter Adrenergic receptor affinity 1=2, 1>>>2 Increased peripheral resistance (vasoconstriction) Increased heart rate and contractility Inhibits lipolysis Slightly stimulates metabolism Slightly stimulates glycogenolysis and gluconeogenesis 82 Adrenal Medulla - Regulation • Stimulation –  Sympathetic NS activity – Exercise, stress – Hypovolemia, hypotension • Inhibition –  Parasympathetic activity 83 Pancreas • Anatomy – Location – long tapered organ behind the stomach and between the duodenum and spleen – Composed of head, body, tail – Arises from GI tract as accessory organ – Has both endocrine and exocrine function 84 Pancreas • Histology – Exocrine – pancreatic acini • secretes digestive juices – Endocrine – Islets of Langerhans • • • •  cells – secretes glucagon and amylin  cells – secretes insulin  cells – secretes somatostatin PP cells – secretes pancreatic polypeptide 85 Insulin • Structure – protein; 2 polypeptide chains linked by 2 disulfide bridges • Synthesis – on ribosomes as preprohormone, then cleaved to prohormone, then to insulin • Transport – unbound • ½ life about 6 minutes in blood • Degraded by insulinase (liver) 86 Insulin • Target cells – All cells except brain – Especially effects liver, skeletal muscle, adipose tissue • Insulin receptor linked to tyrosine kinase which phosphorylates intracellular enzymes, and causes exocytosis of glucose and amino acid translocator proteins 87 Insulin - Effects • Skeletal Muscle – Energy source in skeletal muscle • At rest with little insulin: fatty acids > glucose • During exercise: glucose > fatty acids • At rest with insulin: glucose > fatty acids – Insulin effects • • • • • • •  glucose and a.a. transport  glycogenesis glycogenolysis glycolysis pyruvate  acetyl CoA protein synthesis  proteolysis 88 Insulin Effects • Liver – – – – – – – – glucokinase (glucose trapping)  glycogenesis glycogenolysis (phosphorylase) gluconeogenesis glycolysis pyruvate  acetyl CoA (pyruvate dehydrogenase) lipogenesis (FFA  triglycerides  LDL)  protein synthesis 89 Insulin Effects • Adipose Tissue – glucose transporter – lipoprotein lipase – for transport of fats into adipose cells (triglycerides FFA) – Glucose  glycerol for triglyceride synthesis – lipogenesis – hormone sensitive lipase 90 Insulin Effects • The “Big Picture” – After a meal (especially high carb meals) insulin secretion increases – Generally, cells will increase uptake and utilization of glucose rather than fats – Cells will store glucose as glycogen until storage is maximized (liver, muscle) – About 60% of glucose from meal is stored in liver – Excess glucose will be converted to fat (liver, adipose) – Brain tissue is always permeable to glucose which is its primary energy source ; insulin independent 91 Insulin Effects • Growth – Both growth hormone and insulin promote protein formation and prevents degradation of proteins – Both hormones are necessary for normal growth (synergism) 92 Insulin - Regulation • Stimluates release – – – – Increased blood glucose Increased blood free fatty acids Increased blood amino acids (arginine, lysine) GI hormones (gastrin, cholecystokinin, secretin, gastric inhibitory peptide) – Glucagon, growth hormone, cortisol – Parasympathetic stimulation (Ach) – Insulin resistance (obesity, type II diabetes) 93 Insulin Regulation • Inhibits release – – – – Decreased blood glucose Fasting Somatostatin Catecholamines 94 Insulin Deficiency • Diabetes Mellitus – Type 1 • Insulin dependent (IDDM) • Lack of insulin secretion by pancreas • Autoimmune disease against beta cells (usually) – Type II • Non-insulin dependent (NIDDM) • Decreased sensitivity to insulin (insulin resistance) 95 Type 1 Diabetes mellitus • • • • • • • • • • • Increased blood glucose Glucosurea Polyurea Dehydration Polydipsia Polyphagia with weight loss Blood vessel damage Peripheral neuropathy Hypertension / kidney disease Atherosclerosis ketoacidosis 96 Type II Diabetes Mellitus • • • • • • More common than type I (80-90%) Often associated with obesity Insulin levels increased Mild hyperglycemia Beta cell “exhaustion” Less problem with ketoacidosis than type I 97 Hyperinsulinism • Adenoma of islets of Langerhans (rare) • Insulin “shock” – Insulin causes excessive drop in plasma glucose – Nervous system “starves” – Initially leads to hallucinations, tremors, nervousness – As hypoglycemia progresses, seizures, coma 98 Glucagon • Structure: protein • Effects – Increased glycogenolysis (liver) – Increased gluconeogenesis (liver) – Activates adipose cell lipase 99 Glucagon • Stimulation – Hypoglycemia – Autonomic activation (exercise) – Increased plasma amino acids • Inhibition – Hyperglycemia – Insulin – somatostatin 100 Somatostatin • Structure: polypeptide • Effects – Depress insulin and glucagon secretion – Decreased stomach motility, GI absorption – Extends time over which food is assimilated into tissues • Recall it is also known as the growth hormone inhibitory hormone from the hypothalamus 101 Somatostatin • Stimulation – Increased plasma glucose, amino acid, and FA levels – GI hormones (gastrin, secretin, cholecystokinin, GIP) • Inhibition – Decreased plasma glucose, amino acid, FA levels 102 Calcium & Phosphate Homeostasis • Major Factors influencing Ca and PO4 – – – – – – Parathyroid hormone Calcitonin Vitamin D Intestinal absorption rate Renal excretion rate Bone mineral uptake/release 103 Calcium • ECF concentration very tightly controlled • Ca functions: – – – – – Muscle contraction Nerve impulse transmission Blood clotting Cellular signaling Bone matrix • Hypocalcemia – Tetany – Seisures 104 Calcium • Hypercalcemia – CNS depression – Decreased reflex activity – Constipation • Normal Calcium Distribution – 0.1% in ECF/plasma – 1% in cells – 99% in bones • Plasma Calcium – 50% ionized calcium – 41% protein-bound calcium – 9% Ca complexed to anions 105 Phosphates • Not as tightly controlled • Phosphate distribution – 85% in bones – 14-15% in cells – < 1% in ECF 106 Phosphates • Forms – HPO4-2, H2PO4- depending on pH • Functions – – – – Bone matrix Intracellular buffer Renal tubular buffer Phosphorylation (ATP, enzymes, etc.) • Hyper/hypo phosphatemia – Not generally significant except phosphate depletion may lead to bone demineralization. 107 Calcium Exchange • See figure 79-3 of the text – note the relationship between the following: – – – – – – Dietary intake Intestinal absorption and secretion Excretion in feces Kidney (filtration/reabsorption/excretion) Cell calcium stores Bone (deposition/absorption) 108 Bone • Components: – Osteoid (organic matrix) - Gives tensile strength • Collagen fibers • ground substance – Bone salts – gives compressive strength • Hydroxyapatite crystals Ca10(PO4)6(OH)2 • Non crystaline amorphous substances – CaHPO4.2H2O – Ca3(PO4)2.3H2O • Pyrophosphate – inhibits HAP deposition in tissues other than bone 109 Bone • Calcification – osteoblasts – – – – Osteoid laid down Osteoblasts encased  osteocytes Precipitation of bone salts Woven bone  low HAP, high amorphous salts – Replaced by stronger bone (higher HAP) – Some amorphous salts always there (easily exchanged) 110 Bone • Bone absorption – – – – Osteoclasts (macrophages, multinucleated) Secrete proteolytic enzymes and acid Tunnels into bone Osteoblasts fill in new bone (osteons, Haversian) • Calcification and absorption= remodeling – Old bone is brittle – Bone can respond to stresses 111 Vitamin D • See fig 79-6 in the text – Note the following • Activation cascade of vitamin D • Role of PTH • Inhibitory feedback 112 Vitamin D - Actions • Active form = 1/25 dihydroxycholecalciferol • Actions – – – – Promotes intestinal calcium absorption (calcium binding protein) Promotes phosphate absorption by intestines Decreases renal calcium and phosphate excretion (minor) Bone absorption and bone deposition • excessive Vit. D  bone absorption • Small amts. Vit D  bone calcification • PTH without Vit. D  no absorption 113 Parathyroid Gland • Anatomy – 4 small glands located posterior to the thyroid gland, 2 on the left, 2 on the right • Histology – Chief cells – secretes PTH – Oxyphil cells – function unknown 114 Parathyroid Hormone (PTH) • Protein • Preprohormone  prohormone PTH • Target tissues – Bone – cAMP dependant – Kidneys – cAMP dependant – Intestines – indirectly due to PTH effects on vitamin D 115 Parathyroid Hormone • General Effects (see fig 79-10) – Increases blood Ca+2 levels • Mainly by bone absorption – Decreases blood phosphate levels • Mainly by increase excretion by kidneys 116 Parathyroid Hormone • Effects on bone - bone absorption – Rapid phase (osteolysis) • mediated by osteocytes and osteoblasts (have PTH receptors) • causes release of calcium and phosphorus salts – Slow Phase • mediated by osteoclasts – Activated indirectly via osteocytes/osteoblasts – Stimulate existing ostoclasts and increase development of new osteoclasts • Breaks down osteoid as well as minerals 117 Parathyroid Hormone • Effects on Kidneys – decreases Ca excretion – increases phosphate excretion (which overrides increased phosphate absorption from bone) – Occurs mainly in the distal tubules and collecting tubules – Increases formation of 1, 25 dihydroxycholecalciferol 118 Parathyroid Hormone • Effects on Intestines – Because of the increased activated vitamin D, more calcium and phosphate is absorbed in the intestines • PTH Regulation – Stimulated by decreased ECF Ca+2, histamine, epinephrine – Inhibited by increases ECF Ca+2, calcitonin, 1,25 dihydroxycholecalciferol – Released in diurnal pattern 119 Calcitonin • Peptide released by parafollicular cells of the thyroid gland • Target tissue = bone • Effects – Decrease osteoclast activity – Decrease osteocytic osteolysis – Decrease formation of new osteoclasts • Note- prolonged decreases in osteoclast activity leads to decreased osteoblast activity, therefore no appreciable changes in calcium ion concentration – There is a very weak effect on kidney to increase calcium excretion 120 Hypoparathyroidism • Calcium reabsorption from bones is depressed • ECF Ca+2 levels decrease • Results in tetany • Causes – Autoimmune disorder against parathyroid gland – Thyroid surgery complication – genetic 121 Hyperparathyroidism • • • • • Extreme osteoclastic activity Increases ECF Ca+2 levels Decreased phosphate levels Weakened bones with frequent fractures Cystic bone “osteitis fibrosa cystica” 122 Hyperparathyroidism • High plasma alkaline phosphatase • Depression of the nervous system, muscle weakness, constipation • Metastatic calcification • Kidney stones • Causes – Primary – tumor, autoimmune – Secondary – vitamin D deficiency which leads to hypoclacemia and hypersecretion of PTH • Rickets (child) • Osteomalacia (adult) 123 Male Reproductive System • Anatomy – – – – – – – – – Testis (seminiferous tubules, rete testis) Epididymis (head, body, tail) Vas (ductus) deferens (ampulla) Seminal Vesicle Ejaculatory Duct Urethra (prostatic, membranous, penile) Prostate gland Bulbourethral (Cowper’s) Gland Penis (erectile tissue; corpus cavernosum, spongiosum) 124 Spermatogenesis • Occurs in seminiferous tubules – Spermatogonia – germinal epithelial cells – Sertoli Cells – Primary spermatocyte • First meiotic division – Secondary spermatocyte • Second meiotic division – Spermatid (haploid, 23X or 23Y) – Spermiogenesis – spermatids  mature spermatozoa 125 Spermatozoa • Head – Condensed nucleus – Acrosome (hyaluronidase, proteolytic enzymes) • Tail (flagellum) – Microtubules (axoneme) – Cell membrane – Mitochondria (proximal) 126 Hormonal Control of Spermatogenesis • Testosterone – secreted by Leydig cells – growth and division of germinal cells • Luteinizing hormone – anterior pituitary – stimultes Leydig cells • Follicle-stimulating hormone – anterior pituitary – stimulates Sertoli cells, which aid spermiogenesis • Estrogens – converted from testosterone – aids spermatogenesis • Growth Hormone – promotes early division of spermatogonia 127 Maturation, Storage of Sperm • Epididymis – some storage, develop some motility (inhibited until ejaculation) • Vas deferens – most storage occurs here 128 Semen • Spermatozoa (10%) • Seminal Vesicles (60%) – Fructose, citric acid – Prostaglandins – Fibrinogen • Prostate gland (30%) – Calcium, citrate, phosphate, clotting enzyme, fibrinolysin – Alkaline pH • Bulbourethral gland – Mucus (lubricant) 129 In the Female Reproductive Tract • Capacitation – Final activation of sperm – Occurs in female reproductive tract • Acrosome reaction – Enzymes penetrate the corona radiata (granulosa cells) and zona pellucida surrounding the ovum • Fertilization - union of sperm and ovum pronuclei • Prevention of polyspermy – cortical reaction 130 Factors Affecting Fertility • Temperature – Scrotal reflex – Cryptorchidism • Sperm count – 400 million sperm / ejaculate on average – Decreased sperm count  reduced fertility • Sperm morphology or motility 131 The Male Sexual Act • Stimulation – Sensory stimulation of glans penis and adjacent structures pudendal nerve  sacral plexus  spinal cord  brain – Psychological state – can initiate or inhibit sexual function. 132 The Male Sexual Act • Stages – Penile erection – parasympathetic – Lubrication – parasympathetic, urethral glands and bulbourethral glands – Emission – sympathetic, contraction of vas deferens, ampulla, prostate, seminal vesicles – Ejaculation – sympathetic, addds contraction of ischiocavernosus and bulbocarvernosus, compress erectile tissue – Resolution – sexual excitement ceases 133 Androgens • Includes testosterone, dihydrotestosterone, androstenedione • Formed by the interstitial cells of Leydig, and much less so in the adrenal glands • Steroids derived from cholesterol • Transported by albumin or sex hormone-binding globulin • Most testosterone is converted to dihydrotestosterone upon binding to tissues • Degraded in liver to products excreted in urine 134 Functions of Testosterone • Fetus – 7th week – stimulates male sexual organ development – Release stimulated by hCG – Last trimester – descent of testes • Puberty – Production increases significantly during puberty (stim. by gonadotropic hormones from pituitary) – Stimulates secondary sexual characteristic development (hair,voice) 135 Functions of Testosterone • Other effects – – – – Baldness Acne Muscle development – protein anabolism Bone – increase in mass • Control of Secretion: – GnRH  LH (and FSH)  Leydig cells testosterones 136 Female Reproductive System • Reproductive tract – Vagina – Uterus • Cervix • Body • Fundus – Ovaducts (uterine tubes, Fallopian tubes) • Fimbriae, ampulla, isthmus 137 Ovarian Cycle • Follicular phase (day 1-13) – Primordial follicle – each cycle, 8-12 follicles undergo the following development – Primary follicle – Secondary follicle (vesicular follicle) – Tertiary follicle (mature, Graffian) – Follicle cells • Primary oocyte  secondary oocyte • Granulosa cells – secrete estrogens • thecal cells – secrete some androgens 138 Ovarian Cycle • Ovulation – expulsion of oocyte and corona radiata – Usually only one follicle reaches this stage per cycle – Occurs about day 14 of the female reproductive cycle – Triggered by LH surge (FSH surge less important) • Luteal phase – Development of corpus luteum – Secretes estrogens and progesterone – Ends with involution 139 Uterine Cycle • Day 1-5 – menstrual phase – Due to lack of progesterone (and estrogen) from involuted corpus luteum – Vasospasm of endometrial blood vessels – Necrosis of endometrium – Uterine contractions (prostaglandins) 140 Uterine Cycle • Day 6-13 – proliferative phase – Due mainly to estrogens – Re-epithelialization and growth in thickness • Day 14-26 – Secretory phase – – – – Due mainly to progesterone Endometrial swelling Secretory development Blood vessels and glands become tortuous • Day 27 – Ischemic phase – Lack of nutrients/oxygen due to vasospasm leads to necrosis and menstruation ensues 141 Estrogens • Secreted by ovaries (and adrenal cortex), and placenta • Synthesized from cholesterol • Types – -estradiol (most significant) – Estrone – Estriol • Transport – albumin, estrogen-binding globulins 142 Estrogens - Functions • Reproductive tract – uterus, vagina, oviducts, and external genitalia increase in size – Vaginal epithelium thickens • Breast – – – – Development of stromal tissues of breast Development of extensive duct system Fat deposition In conjunction with prolactin and progesterone  milk production 143 Estrogens - Functions • Skeleton – Increased osteoblastic activity – Union of epiphyses – After menopause, decreased estrogen linked with osteoporosis • Protein deposition – Weakly causes protein anabolism but much less so than testosterone 144 Estrogens - Functions • Fat deposition – In subcutaneous tissues – In breasts – Thighs and buttocks • Hair – Axillary and pubic hair is more due to androgens from adrenal cortex than due to estrogens 145 Estrogens - Functions • Skin – Soft and smooth texture, increases vascularity • Electrolyte balance – Causes sodium and water retention in high amounts (as occurs during pregnancy) 146 Progestins • Secreted by ovaries especially in latter half of ovarian cycle • Synthesized from cholesterol • Types – Progesterone (most important) – 17--hydroxyprogesterone • Transport – albumin and progesterone binding globulins 147 Progesterone - Functions • Uterus – Promote secretory changes in uterus in last ½ of uterine cycle – Decreases uterine smooth muscle activity • Uterine tubes – Increases secretions • Breasts – Lobule and alveoli development – With prolactin  milk secretion 148 Regulation of Female Reproductive Cycle • GnRH – Secreted by the hypothalamus in a pulsitile fashion – Stimulates secretion of FSH and LH • FSH and LH FSH – follicle stimulating hormone LH – luteinizing hormone – stimulates ovulation Estrogen in small amounts inhibits their release Estrogen in large amounts increases release??, or in conjunction with progesterone?  preovulatory surge. – Inhibin secreted by the corpus luteum inhibits release 149 – – – – Puberty and Menarche • Puberty – caused by increase in FSH and LH secreted by the anterior pituitary – Begins at about 8 y.o.a. • Menarche – first menstrual period, 11-16 y.o.a. 150 Menopause • Around 40-50 y.o.a. • “burning out” of the ovaries – decrease in estrogens as number of follicles dwindle. • Symptoms – – – – – – Hot flashes Dyspnea Irritability Fatigue Anxiety Decreased strength and calcification of bones 151 Maturation of Ovum • Ovary – Primary oocyte in follicle – Secondary oocyte following meiosis I • Generation of first polar body – Ovulation • Ovum + granulosa cells (corona radiata) • Begin but not finish meiosis II – Entrance into oviduct • Fimbriated end – cilia activated by estrogen • Travel to ampulla of oviduct 152 Fertilization • Sperm transport – Sperm motility (flagellum) – Uterine and oviduct contractions • Prostaglandins in semen • Oxytocin release in female during intercourse – Sperm reach ampulla = typical site for fertilization 153 Fertilization • Steps in fertilization – Acrosome reaction (sperm) digest corona radiata and zona pellucida – Fusion of sperm and ovum membranes – Ovum response • Complete meiosis II, form second polar body • Zona reaction – prevents polyspermy – Fusion of male and female pronucei – restore diploid number • Sex determination – XX vs. XY 154 Zygote/blastocyst Transport • 3-5 days • Fluid current – ovaduct epithelial secretions and cilia • Zygote undergoes cleavage divisions to form morula, then blastocyst. • Ovaduct secretions provide nutrition to zygote/blastocyst 155 Implantation • 5-7 days post ovulation • Uterine “milk” • Trophoblast cells secrete proteolytic enzymes  burrow into uterine epithelium • Trophoblast + uterine tissue  placental development 156 Nutrition of Embryo • Endometrial glands store glycogen, protein, lipids in “decidual cells” • Digested and absorbed by trophoblast (syncytiotrophoblast) • Progesterone maintains endometrium, and promotes gland secretion • So called “trophoblastic nutrition” last about 8 weeks until substantial placental development has taken place. 157 Nutrition of Embryo/Fetus • Placenta (begins functioning about 8 weeks post fertilization) • Trophoblastic cords (syncytiotrophoblast) allow penetration of maternal blood vessels • Maternal blood fills spaces called lacunae (sinuses) • Cytotrophoblast develops into villi containing embryonic/fetal blood vessels • Formation of maternal blood – fetal blood barrier 158 Placental Transfer • Oxygen – Simple diffusion – O2 gradient • Maternal PO2 = 50 mm Hg • Fetal PO2 = 30 mm Hg – Hemoglobin saturation in fetus remains high despite low partial pressure of O2 because: • Hemoglobin F – higher affinity (O2-Hb curve is further to the left) • High concentration of fetal Hb • Bohr effect – as CO2 (and acid) is transferred to mother, HbF binds more oxygen, and HbA (mother) binds less O2. • CO2 – simple diffusion 159 Placental Transfer • Nutrients – Facilitated diffusion (especially glucose) – Simple diffusion (most nutrients, electrolytes) • Waste – Simple diffusion of urea, uric acid, creatinine etc. 160 Hormones and Pregnancy • Human chorionic gonadotropin (hCG) – Secreted by syncytiotrophoblast cells of the embryo starting at implantation – Serum levels are highest at about 10-12 weeks of pregnancy, then taper off – glycoprotein 161 Human Chorionic Gonadotropin • Functions – Prevents involution of corpus luteum • Corpus secretes more progesterone and estrogen • Prevents menstruation • Decidua cells swell – Stimulates interstitial cell development in male fetuses • Secretes more testosterone • Male develops male sex organs 162 Placental Estrogens • Secreted by syncytiotrophoblast • Toward end of pregnancy, estrogen is 30X normal • Function – Enlargement of mother’s uterus – Enlargement of mother’s breasts and growth of breast ducts – Enlargement of external genitalia – Relaxation of SI and pubic joint ligaments – Mitogenic effect on fetus 163 Placental Progesterones • Secreted by syncytiotrophoblast • Secretory rate 10X normal • Replaces corpus luteum as primary source of estrogens • Functions – Decidual cell development in endometrium – Decreases contractility of pregnant uterus – Promotes breast development 164 Human Chorionic Somatomammotropin (hCS) • a.k.a. human placental lactogen • Secreted by placenta starting at 5th week • Functions (not well known) – May aid breast development – May have similar effects to growth hormone – Decreases insulin sensitivity in mother 165 Relaxin • Secreted by ovaries and placenta in response to hCG • Relaxes ligaments of symphysis pubis, may cause cervix effacement. 166 Endocrine Alterations in Pregnancy • Pituitary – enlarges, increases corticotropin, thyrotropin, and prolactin production • Adrenal cortex – increased glucocorticoids, aldosterone • Thyroid – increased thyroxine • Parathyroid – increased parathormone 167 Pregnancy • Weight gain – Average 24 lbs • • • • • 7 lbs fetus 4 lbs amniotic fluid, placenta, fetal membranes 2 lbs uterus 6 lbs blood, extracellular fluid 3 lbs fat – Increase in appetite – can increase weight gain even more if mother isn’t careful. 168 Pregnancy • Increased metabolic rate • Nutrition – Iron –for baby and mother’s extra blood – Vitamin D – for calcium – Vitamin K – for clotting factors • Increased blood volume (1-2 liters) • Increased CO 169 Pregnancy • Increased respiratory rate (due to increased metabolism as well as effects of uterus against diaphragm) • Amniotic fluid – From fetal renal excretion – Amniotic membrane – Turnover every 3 hours 170 Preeclampsia, Eclampsia • • • • • Hypertension, proteinurea Excess salt and water retention Arterial spasm in kidneys, brain, and liver Due to hormones?, autoimmunity?, allergy? Eclampsia (coma, death) is severe form of preeclampsia that occurs shortly before birth 171 Parturition • Increase in uterine activity – – – – Estrogen/progesterone ratio Oxytocin Stretch of uterine smooth muscle Cervical stretch/irritation • Braxton Hicks contractions – weak periodic contractions before true labor begins • Labor – Positive feedback??? – Cervix pressure = reflex uterine contractions , pituitary secretion of oxytocin  172 Parturition • Abdominal muscle – reflexively contract due to painful stimuli from uterus and birth canal. • Stages of labor – First – cervical dilation and effacement – (8-24 hours w/ first pregnancy), amnion rupture – Second – movement of fetus through cervix and vagina (30 min – 2 hrs w/ first pregnancy) • Uterine involution – Lasts 4-5 weeks, facilitated by lactation 173 Lactation • Growth of ductal system – estrogen (and other hormones GH, prolactin, glucocorticoids, insulin) • Lobule-Alveolar system – progesterone • Initiation of lactation – prolactin, human chorionic somatomammotropin – Colostrum (proteins, lactose, little fat) – secreted immediately before and after parturition – Milk – after estrogens and progesterones decrease post partum. • Nursing – stimulates prolactin secretion, maintains milk production 174 Lactation • Suppresses female ovarian cycles – Inhibits GnRH secretion from hypothalamus • Ejection (“let down”) – Oxytocin – suckling or emotional signals increase oxytocin secretion from posterior pituitary. • Milk composition – water, fat, lactose, casein, lactalbumin, ash (minerals), antibodies, neutrophils, macrophages 175 Fetal Physiology • Growth – 1st two weeks – placental , membrane development >>>> embryo development – Thereafter, length is roughly proportionate to age – The rate of weight gain increases with age of fetus • Circulatory system – Heart begins beating at about 21 days – Red cells – yolk sac and placenta  liver  spleen bone marrow 176 Fetal Physiology • Respiratory System – Lungs are collapsed – Some respiratory movements, mostly inhibited • Nervous system – 3-4 month – reflexes – Myelinization – complete after 1st year of life 177 Fetal Physiology • GI tract – Ingest and absorb amniotic fluid – Meconium – mucus, bile, amniotic residue • Kidneys – Excretes urine during last half of pregnancy – Control of electrolyte and acid/base balance is poor 178 Fetal Physiology • Metabolism – Mainly utilize glucose for energy – Storage of fat and protein (from glucose sources) – Calcium and Phosphate - most is accumulated during ossification (last 4 weeks of gestation) – Iron – accumulates rapidly for hemoglobin synthesis – Vitamins B12 and folate – for RBC, nervous system, growth Vitamin C – for bone matrix and connective tissue Vitamin D – bone growth (calcium absorption by mother) Vitamin E – function unclear, deficiency leads to spontaneous abortion • Vitamin K – blood clotting 179 • • • • Time of Birth • Onset of breathing – Slightly asphyxiated state during birth – Sensory stimuli from cooled skin at birth – Hypoxia can occur due to compression of umbilical cord, placental separation, anesthesia, excessive uterine contractions – Infant can tolerate up to 10 minutes without O2 – Lung Expansion – requires 60 mm Hg negative pressure to inflate lungs the first time, by 40 minutes, respiration is near normal – Respiratory distress syndrome – prematurity and lack of surfactant 180 Time of Birth • Changes in circulation – Systemic circulation – increased vascular resistance due to loss of circulation through placenta – Pulmonary circulation – decreased vascular resistance due to lung expansion, increased O2 also causes vasodilation of pulmonary vessels – Closure of foramen ovale – due to above pressure changes – Closure of ductus arteriosus – pressure changes reverse blood flow through ductus, and increases oxygen and prostaglandins cause constriction – Closure of ductus venosus – forces more blood through liver sinusoids (prepares liver for functional activity) 181 Nutrition of Neonate • Glucose stores are low • Liver function low (little gluconeogenesis) • Infants use stored fat and protein for energy until mothers milk “comes in” • Neonates typically lose 20% of their weight the first 2-3 days of life (mostly fluid). 182 Miscellaneous Problems • Neonatal jaundice – Bilirubin is not efficiently removed from the blood by the liver (mild jaundice) – Erythroblastosis fetalis – hemolytic anemia increases bilirubin load (severe jaundice) • Renal function – immaturity of kidneys, rapid fluid turnover, high metabolic rate may lead to acidosis and dehydration 183 Miscellaneous Problems • Liver immaturity – – – – Little bilirubin conjugation (see above) Little plasma protein production  edema Deficient gluconeogenesis  low blood glucose Little blood clotting factors  abnormal coagulation • Body temperature – Surface area/ volume ratio  loss of body heat • Immunity – Passive immunity from mother (lasts 6 months) 184 Growth and Development • • • • • • • • • • • • • Birth – suckling 1 month – smiles 2 months – vocalization (other than crying) 3 months – head control 3 ½ months – hand control 5 months – roll over 6 months – sitting 7 ½ month – crawling 8 months – well developed grasp 9 months – pulls up 10 months – walks with support 11 months – stands alone 11 ½ - 12 months - walks alone 185