Differences Between Autocrine, Paracrine, and Endocrine Signaling PDF

**Differences Between Autocrine, Paracrine, and Endocrine Signaling** - **Autocrine Signaling**: - **Mechanism**: Cells release chemical signals (like cytokines or growth factors) that bind to receptors on their own surface or inside themselves. - **Detailed Example*...

**Differences Between Autocrine, Paracrine, and Endocrine Signaling** - **Autocrine Signaling**: - **Mechanism**: Cells release chemical signals (like cytokines or growth factors) that bind to receptors on their own surface or inside themselves. - **Detailed Example**: - **Interleukin-1 in immune cells**: Macrophages produce IL-1, which binds to IL-1 receptors on the same macrophages to enhance their immune activity. - **Cancer cells**: Often rely on autocrine signaling for rapid growth; for instance, some breast cancers overproduce growth factors like **epidermal growth factor (EGF)**, which acts on their own EGF receptors to drive growth. - **Paracrine Signaling**: - **Mechanism**: Cells secrete local mediators, such as neurotransmitters or nitric oxide, affecting nearby cells without entering circulation. - **Detailed Example**: - **Synaptic transmission**: Neurons release neurotransmitters (e.g., serotonin, dopamine) across synaptic gaps to neighboring neurons, influencing nerve impulses. - **Nitric oxide in blood vessels**: Endothelial cells release NO, which diffuses to nearby smooth muscle cells, causing relaxation and vasodilation. - **Endocrine Signaling**: - **Mechanism**: Specialized glands release hormones into the bloodstream, reaching target cells throughout the body. - **Detailed Example**: - **Insulin from pancreatic beta cells**: Regulates glucose uptake in distant cells (muscle, fat). - **Thyroid hormones (T3 and T4)**: Control metabolism in nearly all body tissues, from regulating heart rate to influencing digestion. **2. Major Hormone Classes and Their Signaling Mechanisms** - **Peptide Hormones**: - **Characteristics**: Water-soluble, composed of amino acid chains, ranging from short peptides (ADH) to longer proteins (GH). - **Receptor Binding and Action**: Bind to membrane-bound receptors; signal transduction often involves **G-protein coupled receptors** (GPCRs) or **tyrosine kinase receptors**. - **Example Mechanism**: - **Insulin Signaling Pathway**: - Binds to tyrosine kinase receptor on the cell membrane. - Activates PI3K/AKT pathway, promoting glucose transporters (GLUT4) to cell surface, allowing glucose uptake. - **Steroid Hormones**: - **Characteristics**: Lipophilic, synthesized from cholesterol, enabling them to pass through cell membranes. - **Receptor Binding and Action**: Bind to intracellular receptors (cytoplasmic or nuclear), forming a complex that enters the nucleus to directly regulate gene expression. - **Example Mechanism**: - **Cortisol**: - Binds to glucocorticoid receptor in the cytoplasm. - Translocates to nucleus, binds DNA, and influences transcription of anti-inflammatory proteins and enzymes for gluconeogenesis. - **Amine Hormones**: - **Characteristics**: Derived from single amino acids (e.g., tyrosine for catecholamines, tryptophan for melatonin). - **Receptor Binding and Action**: Either cell-surface receptors (e.g., adrenergic receptors for adrenaline) or intracellular receptors (e.g., thyroid hormone receptors). - **Example Mechanism**: - **Adrenaline**: Binds to adrenergic receptors, activates cAMP second messenger pathway, and increases heart rate and glucose release. **3. Primary and Secondary Endocrine Organs and Their Hormones** - **Primary Endocrine Organs**: - **Hypothalamus**: - Produces regulatory hormones that control the pituitary: **CRH** (corticotropin-releasing hormone), **GnRH** (gonadotropin-releasing hormone), and **TRH** (thyrotropin-releasing hormone). - **Vasopressin (ADH)**: Regulates water reabsorption in kidneys. - **Pituitary Gland**: - **Anterior Pituitary Hormones**: - **ACTH** (adrenocorticotropic hormone): Stimulates adrenal cortex for cortisol production. - **FSH** and **LH**: Regulate reproductive processes. - **Posterior Pituitary Hormones**: - **Oxytocin**: Facilitates childbirth, lactation. - **Adrenal Cortex**: Produces aldosterone, cortisol, and androgens. - **Thyroid Gland**: Produces T3 and T4, which regulate metabolic rate. - **Pancreas**: - Produces insulin (beta cells) for lowering blood glucose and glucagon (alpha cells) for increasing glucose. - **Secondary Endocrine Organs**: - **Kidneys**: Secrete erythropoietin to stimulate red blood cell production. - **Heart**: Produces ANP (atrial natriuretic peptide) to decrease blood pressure by influencing kidney function. - **GI Tract**: Releases gastrin, CCK (cholecystokinin), and ghrelin, influencing digestion and appetite. **4. Endocrine and Neuroendocrine Reflex Regulation of Homeostasis** - **Neural Reflex Regulation**: - **Mechanism**: Direct stimulation by the autonomic nervous system. - **Example**: The adrenal medulla releases adrenaline upon sympathetic nervous activation during stress, leading to increased heart rate and glucose availability. - **Humoral Reflex Regulation**: - **Mechanism**: Blood levels of ions or nutrients directly influence hormone secretion. - **Example**: Low calcium levels trigger parathyroid hormone (PTH) release, increasing calcium reabsorption in kidneys and release from bones. - **Hormonal Reflex Regulation**: - **Mechanism**: Hormone levels are regulated through hierarchical feedback loops. - **Example**: The HPA axis, where CRH from the hypothalamus stimulates ACTH release from the pituitary, which in turn stimulates cortisol release from the adrenal cortex. High cortisol levels inhibit further CRH and ACTH release. **5. Hypothalamus and Pituitary Glands: Structure, Hormones, and Function** - **Hypothalamus**: - Located above the pituitary in the brain, serving as the master controller. - **Releases**: Hormones that control the pituitary's release of hormones like TSH, ACTH, and growth hormone. - **Pituitary Gland**: - **Anterior Pituitary**: Synthesizes hormones such as ACTH (stimulates cortisol release), TSH (stimulates thyroid), and GH (promotes growth). - **Posterior Pituitary**: Stores and releases ADH (antidiuretic hormone for water retention) and oxytocin (for childbirth and lactation). **6. GH/IGF-1 Axis and Its Life-Stage Specific Effects** - **GH**: Produced by anterior pituitary; stimulates IGF-1 production in the liver. - **Life-Stage Effects**: - **Children**: GH and IGF-1 promote growth in long bones and muscles. - **Adults**: Maintain muscle mass, bone density, and support metabolism. - **Hypo-function**: Can lead to dwarfism in children; decreased muscle mass in adults. - **Hyper-function**: Causes gigantism in children (excessive height) and acromegaly in adults (bone and tissue thickening). **7. Factors Influencing Hormone Concentrations and Assessing Disorders** - **Factors**: - **Circadian Rhythms**: Hormones like cortisol peak in the morning. - **Health Conditions**: Conditions like hypothyroidism lower thyroid hormone levels. - **Medications**: Drugs can increase or decrease hormone levels. - **Assessments**: - **Blood Tests**: Check levels of hormones like TSH, cortisol, etc. - **Imaging**: MRI or CT to assess gland size and structure. - **Function Tests**: Dexamethasone suppression test for Cushing's syndrome. **8. Thyroid and Parathyroid Glands: Structure and Embryology** - **Thyroid Structure**: Contains follicles filled with colloid, where thyroglobulin binds iodine to produce T3 and T4. - **Parathyroid Structure**: Small glands behind the thyroid, producing PTH for calcium regulation. - **Embryological Origins**: - Thyroid from endodermal tissue at the base of the tongue. - Parathyroids from pharyngeal pouch endoderm. **9. Thyroid Hormone Synthesis and Regulation** - **Process**: - **Iodine uptake** into follicular cells. - Tyrosine molecules in thyroglobulin are iodinated, forming T3 and T4. - TSH stimulates endocytosis of colloid, releasing T3/T4 into blood. - **Regulation**: - Negative feedback from T3/T4 inhibits further TSH and TRH release. **10. Thyroid Hormone Role in Metabolism** - **Effects**: - Stimulates basal metabolic rate, increasing oxygen consumption. - Influences heart rate, GI motility, and muscle function. - Essential for fetal and childhood brain development. **Thyroid and Parathyroid Glands in Calcium and Phosphate Homeostasis** - **Thyroid's Role via Calcitonin**: - **Calcitonin**: Produced by parafollicular (C-cells) in the thyroid; released in response to high blood calcium levels. - **Actions**: - Inhibits osteoclast activity in bones, reducing bone resorption and lowering calcium release into the bloodstream. - Increases calcium excretion in the kidneys, promoting a decrease in blood calcium levels. - **Regulation**: Primarily regulated by blood calcium levels in a negative feedback mechanism. Calcitonin has a lesser role in adults compared to children, where it is more active in regulating calcium levels. - **Parathyroid's Role via Parathyroid Hormone (PTH)**: - **Parathyroid Hormone (PTH)**: Released by chief cells in the parathyroid gland in response to low blood calcium levels. - **Actions**: - **Bones**: Stimulates osteoclasts to break down bone matrix, releasing calcium and phosphate into the blood. - **Kidneys**: Increases calcium reabsorption while promoting phosphate excretion to prevent precipitation of calcium phosphate crystals. - **Vitamin D Activation**: Stimulates the conversion of vitamin D to its active form (calcitriol) in the kidneys, enhancing intestinal calcium absorption. - **Regulation**: Controlled by calcium-sensing receptors on parathyroid cells, adjusting PTH release based on calcium levels. **12. Adrenal Glands: Structure and Hormones** - **Macrostructure**: Located above each kidney, composed of two main regions: - **Adrenal Cortex**: - **Zona Glomerulosa**: Outer layer; produces mineralocorticoids (mainly **aldosterone**). - **Zona Fasciculata**: Middle layer; produces glucocorticoids (mainly **cortisol**). - **Zona Reticularis**: Inner layer; produces androgens. - **Adrenal Medulla**: Inner region that produces catecholamines (**adrenaline and noradrenaline**) as part of the sympathetic nervous response. - **Functions of Key Hormones**: - **Aldosterone**: - Acts on the kidneys to increase sodium reabsorption and potassium excretion, indirectly increasing water retention and blood pressure. - **Cortisol**: - A stress hormone that regulates glucose metabolism, supports immune modulation, and helps with fat and protein breakdown. - **Adrenaline and Noradrenaline**: - Mediate the "fight or flight" response by increasing heart rate, blood pressure, and blood glucose levels for rapid energy mobilization. **13. Regulatory Systems Controlling Adrenal Hormone Production** - **HPA (Hypothalamic-Pituitary-Adrenal) Axis**: - **CRH** (Corticotropin-releasing hormone) from the hypothalamus stimulates ACTH production in the anterior pituitary. - **ACTH** triggers cortisol release from the adrenal cortex. Elevated cortisol levels provide negative feedback, inhibiting further CRH and ACTH release. - **RAAS (Renin-Angiotensin-Aldosterone System)**: - **Renin** released by the kidneys in response to low blood pressure or sodium levels converts angiotensinogen to angiotensin I. - **Angiotensin I** is converted to angiotensin II in the lungs, which stimulates aldosterone release from the adrenal cortex, increasing blood volume and pressure. - **Sympathetic Nervous System**: - Directly stimulates the adrenal medulla to release adrenaline and noradrenaline in response to stress, trauma, or hypoglycemia, facilitating an immediate response. **14. Pancreatic Hormones: Insulin, Glucagon, and Amylin in Glucose Homeostasis** - **Insulin**: - **Produced by beta cells** in the islets of Langerhans in response to high blood glucose. - **Mechanism of Action**: - Promotes glucose uptake into cells (primarily muscle and adipose tissues) by increasing the translocation of GLUT4 transporters to the cell surface. - Stimulates glycogenesis (glucose storage as glycogen) in the liver and muscle. - Inhibits gluconeogenesis (new glucose production) and lipolysis (fat breakdown). - **Effects**: Lowers blood glucose and prevents hyperglycemia. - **Glucagon**: - **Produced by alpha cells** in response to low blood glucose. - **Mechanism of Action**: - Stimulates glycogenolysis (breakdown of glycogen to glucose) and gluconeogenesis in the liver. - Mobilizes stored energy to increase blood glucose levels. - **Effects**: Raises blood glucose, preventing hypoglycemia. - **Amylin**: - **Co-secreted with insulin by beta cells**. - **Mechanism of Action**: - Slows gastric emptying, reducing the postprandial (post-meal) rise in blood glucose. - Suppresses glucagon secretion to fine-tune blood glucose control. - **Effects**: Complements insulin to stabilize blood glucose after meals. **15. Feedback Mechanisms Regulating Pancreatic Hormone Production** - **Neural Regulation**: - Parasympathetic activity (e.g., vagus nerve stimulation) during feeding enhances insulin secretion in preparation for glucose intake. - **Humoral Regulation**: - Blood glucose levels directly regulate insulin and glucagon release; high glucose promotes insulin release, while low glucose stimulates glucagon. - **Hormonal Regulation**: - Incretins (GLP-1 and GIP) from the gut amplify insulin release in response to food intake. **16. Gastrointestinal Hormones in Glycemic Control** - **GLP-1 (Glucagon-like peptide-1)**: - Secreted by L cells in the intestines in response to food. - Increases insulin secretion, decreases glucagon release, and slows gastric emptying to moderate blood glucose spikes. - **GIP (Gastric Inhibitory Polypeptide)**: - Released by K cells in the intestines. - Primarily stimulates insulin release in response to glucose intake, aiding in glucose homeostasis. **17. Diabetes Mellitus: Type I vs. Type II** - **Type I Diabetes**: - An autoimmune condition where the immune system destroys beta cells, leading to complete insulin deficiency. - Symptoms include weight loss, polyuria, and polydipsia. - Treatment requires insulin injections or an insulin pump. - **Type II Diabetes**: - Characterized by insulin resistance in target tissues and a relative decline in insulin production over time. - Associated with obesity, poor diet, sedentary lifestyle, and genetics. - Managed with lifestyle changes, oral medications (e.g., metformin), and sometimes insulin. **18. Androgen Production and Regulation in Males** - **Production**: - **Leydig cells** in the testes produce testosterone, stimulated by LH from the anterior pituitary. - Androgens influence the development and maintenance of male reproductive tissues, muscle growth, and secondary sexual characteristics. - **Regulation**: - **GnRH** from the hypothalamus stimulates the release of LH and FSH. - **Negative Feedback**: Elevated testosterone inhibits GnRH and LH secretion, maintaining hormone balance. **19. Role of Androgens in Male Development and Reproductive Function** - **Primary Sex Characteristics**: Development of testes, penis, and prostate. - **Secondary Sex Characteristics**: Growth of facial and body hair, deepening of the voice, increased muscle mass, and libido. - **Spermatogenesis**: Androgens stimulate sperm production in the seminiferous tubules, critical for male fertility. **20. Oogenesis and Ovarian Cycle (Follicular, Ovulatory, Luteal Phases)** - **Follicular Phase**: - FSH stimulates follicle development in the ovaries. - Dominant follicle matures, producing estrogen, which promotes endometrial growth. - **Ovulation**: - LH surge triggers the release of the mature egg from the follicle. - **Luteal Phase**: - Corpus luteum forms and secretes progesterone, preparing the endometrium for potential embryo implantation. - If fertilization does not occur, the corpus luteum degenerates, leading to menstruation. **21. Endometrial Changes During the Uterine Cycle** - **Menstrual Phase**: Shedding of the endometrial lining if no pregnancy occurs. - **Proliferative Phase**: Estrogen from growing follicles stimulates endometrial regrowth. - **Secretory Phase**: Progesterone from the corpus luteum maintains and thickens the endometrium, preparing it for implantation. **22. Female Reproductive Hormones and Regulation** - **Estrogen**: Produced by ovarian follicles; promotes development of reproductive organs, endometrial growth, and secondary characteristics. - **Progesterone**: Produced by the corpus luteum; maintains the endometrium for implantation and pregnancy. **23. Amenorrhea and Causes** - **Primary Amenorrhea**: Failure to start menstruation by age 16 due to genetic or endocrine disorders. - **Secondary Amenorrhea**: Absence of menstruation after onset, often due to stress, hormonal imbalance, or health conditions like PCOS or hypothyroidism. **24. Influence of Genetics, Hormones, Environment, and Psychosocial Factors on Systems Development and Phenotype (Including Disease)** - **Genetics**: - **Genotype** (individual's genetic makeup) directly impacts physical and biochemical traits (phenotype). - **Epigenetics**: Environmental factors can modify gene expression without altering the DNA sequence (e.g., methylation). - **Examples**: Genetic predispositions to diseases like type II diabetes, hypertension, and certain cancers. - **Hormones**: - Act as **biological signals** to regulate growth, development, and metabolism. - Critical during **puberty** and **pregnancy** for secondary sexual characteristics and reproductive function. - **Diseases**: Hormonal imbalances (e.g., hypothyroidism) can significantly alter physical traits and increase disease risk. - **Environment**: - Includes exposure to toxins, diet, and lifestyle factors (e.g., smoking). - **Nutrition**: Plays a key role in development (e.g., vitamin D for bone growth). - **Example**: Fetal alcohol syndrome results from prenatal alcohol exposure, leading to developmental abnormalities. - **Psychosocial Influences**: - **Stress** can influence hormone levels, such as cortisol, affecting metabolism and immune function. - Social and psychological factors can affect development and risk for conditions like depression and cardiovascular diseases. **25. Major Events in the Development of the Urogenital System** - **Early Embryonic Development**: - **Pronephros**: First kidney structure, non-functional and transient. - **Mesonephros**: Temporary structure in embryo, contributes to reproductive ducts. - **Metanephros**: Develops into the permanent kidney. - **Differentiation of Reproductive System**: - **Indifferent Gonads**: Develop into testes or ovaries based on presence of SRY gene on Y chromosome. - **Wolffian Ducts**: Develop into male reproductive structures (epididymis, vas deferens) if exposed to testosterone. - **Müllerian Ducts**: Develop into female structures (fallopian tubes, uterus) if not suppressed by anti-Müllerian hormone. - **Ascent of the Kidneys**: - Kidneys initially form in the pelvis and ascend to their adult position in the lumbar region. - **Formation of External Genitalia**: - Genital tubercle, urogenital folds, and labioscrotal swellings differentiate under hormonal influence. **26. Fetal Structures and Their Adult Derivatives** - **Kidneys**: Develop from metanephros and become functional in the fetus by the second trimester. - **Mesonephric (Wolffian) Ducts**: - Form male structures like the vas deferens, epididymis, and seminal vesicles. - **Paramesonephric (Müllerian) Ducts**: - Develop into female reproductive structures, including the fallopian tubes, uterus, and upper vagina. - **Urogenital Sinus**: - Gives rise to bladder and parts of the urethra in both sexes. - **Genital Tubercle**: - Forms glans penis in males and clitoris in females. - **Labioscrotal Swellings**: - Form scrotum in males and labia majora in females. **27. Common Developmental Abnormalities of the Urogenital System** - **Cryptorchidism**: Failure of one or both testes to descend, leading to infertility risks if untreated. - **Hypospadias**: Urethral opening on the underside of the penis due to incomplete fusion of the urogenital folds. - **Renal Agenesis**: Absence of one or both kidneys; unilateral agenesis may go unnoticed, while bilateral is fatal without intervention. - **Ectopic Kidney**: Kidneys fail to ascend properly, sometimes remaining in the pelvis. - **Horseshoe Kidney**: Fusion of the lower poles of the kidneys, often asymptomatic but prone to urinary obstruction. - **Congenital Adrenal Hyperplasia**: Genetic disorder affecting steroidogenesis, leading to excess androgen production and ambiguous genitalia in females. **28. Process of Spermatogenesis and Its Histological Correlates** - **Spermatogenesis**: - Occurs in the seminiferous tubules of the testes. - **Stages**: 1. **Spermatogonia** (stem cells) undergo mitosis to form primary spermatocytes. 2. **Primary Spermatocytes** undergo meiosis I to become secondary spermatocytes. 3. **Secondary Spermatocytes** undergo meiosis II to form spermatids. 4. **Spermatids** mature into spermatozoa through spermiogenesis. - **Histological Correlates**: - **Sertoli Cells**: Provide structural and nutritional support to developing sperm cells. - **Leydig Cells**: Located in interstitial space, produce testosterone to support spermatogenesis. - **Lumen**: Contains mature spermatozoa ready for release. **29. Structural Components of the Male Genitourinary System and Their Functions** - **Testes**: Produce sperm and testosterone. - **Epididymis**: Stores and matures sperm. - **Vas Deferens**: Transports sperm during ejaculation. - **Seminal Vesicles**: Secrete fluid rich in fructose for sperm energy. - **Prostate Gland**: Produces fluid that increases sperm motility and viability. - **Penis**: Organ for sexual intercourse and urination. **30. Structural Organization of the Male Abdomino-Pelvic Wall** - **Muscles**: - **Rectus Abdominis**: Flexes trunk and stabilizes pelvis. - **External and Internal Obliques**: Rotate and laterally flex trunk. - **Transversus Abdominis**: Compresses abdominal contents. - **Inguinal Canal**: - Passage for spermatic cord in males. - Common site for hernias due to natural weakness. - **Pelvic Floor Muscles**: - Support pelvic organs; includes levator ani and coccygeus. **31. Common Developmental Conditions of the Male Reproductive System** - **Undescended Testes (Cryptorchidism)**: - Leads to infertility and increased cancer risk if untreated. - **Hypospadias**: Urethral opening located on the underside of the penis. - **Varicocele**: Enlargement of the veins within the scrotum, which can impact fertility. - **Testicular Torsion**: Twisting of the spermatic cord, cutting off blood supply to the testes; a surgical emergency. **32. Structural Components of the Female Internal and External Genital Organs** - **Internal Genitalia**: - **Ovaries**: Produce oocytes and secrete estrogen and progesterone. - **Fallopian Tubes**: Transport oocyte from ovary to uterus; site of fertilization. - **Uterus**: - Layers: **Endometrium** (sheds during menstruation), **Myometrium** (muscle layer for contractions), **Perimetrium** (outer layer). - Supports fetal development. - **Cervix**: Lower portion of the uterus, opens into the vagina; secretes mucus to facilitate or prevent sperm entry. - **Vagina**: Muscular canal for sexual intercourse, menstrual flow, and childbirth. - **External Genitalia** (Vulva): - **Labia Majora and Minora**: Protect internal genital organs. - **Clitoris**: Erectile tissue with sensory functions. - **Vestibular Glands (e.g., Bartholin's Glands)**: Secrete lubrication. ### 33. Blood Supply, Venous and Lymphatic Drainage, and Nerve Supply of the Female Reproductive System - **Blood Supply**: - **Ovaries**: - **Ovarian Arteries**: Branches of the abdominal aorta; enter ovaries via suspensory ligament. - **Anastomose** with uterine arteries. - **Uterus**: - **Uterine Arteries**: Branches of internal iliac arteries. - **Arcuate Arteries**: Within the myometrium. - **Radial Arteries**: Penetrate endometrium. - **Vagina**: - **Vaginal Arteries**: Branches of internal iliac arteries. - **Additional Supply**: From uterine and internal pudendal arteries. - **Venous Drainage**: - **Ovarian Veins**: - **Right Ovarian Vein**: Drains into the inferior vena cava. - **Left Ovarian Vein**: Drains into the left renal vein. - **Uterine and Vaginal Veins**: - Form plexuses draining into internal iliac veins. - **Lymphatic Drainage**: - **Ovaries and Uterine Tubes**: - Drain into para-aortic (lumbar) lymph nodes. - **Uterus**: - **Fundus**: Drains to para-aortic and superficial inguinal nodes. - **Body and Cervix**: Drain to internal and external iliac nodes. - **Vagina**: - Upper third drains to internal and external iliac nodes. - Middle third drains to internal iliac nodes. - Lower third drains to superficial inguinal nodes. - **Nerve Supply**: - **Autonomic Innervation**: - **Sympathetic**: From hypogastric plexus; regulates vasoconstriction. - **Parasympathetic**: From pelvic splanchnic nerves (S2-S4); stimulates glandular secretion. - **Sensory Innervation**: - **Uterine Body and Cervix**: Visceral afferents accompany sympathetic fibers. - **Vagina**: Lower third has somatic innervation via pudendal nerve; sensitive to touch and temperature. **34. Functions of the Female Genital Organs Regarding Their Histology** - **Ovaries**: - **Histology**: - **Germinal Epithelium**: Outer layer of simple cuboidal cells. - **Cortex**: Contains follicles at various stages. - **Medulla**: Contains blood vessels and connective tissue. - **Function**: - Oogenesis: Production of oocytes. - Hormone Secretion: Estrogen and progesterone. - **Fallopian Tubes**: - **Histology**: - **Mucosa**: Ciliated columnar epithelium; aids in oocyte transport. - **Muscularis**: Smooth muscle layers for peristalsis. - **Serosa**: Outer connective tissue layer. - **Function**: - Capture of oocyte after ovulation. - Site of fertilization. - **Uterus**: - **Histology**: - **Endometrium**: - **Functional Layer**: Sheds during menstruation. - **Basal Layer**: Regenerates the functional layer. - **Glands**: Secrete uterine milk to nourish embryo. - **Myometrium**: Thick smooth muscle; contracts during labor. - **Function**: - Implantation site for embryo. - Supports fetal development. - **Vagina**: - **Histology**: - **Mucosa**: Non-keratinized stratified squamous epithelium. - **Muscularis**: Smooth muscle layer. - **Adventitia**: Connective tissue with elastic fibers. - **Function**: - Receives penis during intercourse. - Passageway for childbirth. - **External Genitalia**: - **Histology**: - **Labia Majora and Minora**: Skin folds with sebaceous and sweat glands. - **Clitoris**: Erectile tissue with abundant nerve endings. - **Function**: - Protection of internal genitalia. - Sexual arousal. **35. Pelvic Bony Features Important in Parturition** - **Pelvic Girdle**: - Comprised of two hip bones (ilium, ischium, pubis), sacrum, and coccyx. - **Pelvic Brim (Inlet)**: - **Boundaries**: - Sacral promontory. - Arcuate line of ilium. - Pectineal line of pubis. - Pubic symphysis. - **Importance**: Determines size and shape of birth canal entrance. - **Pelvic Outlet**: - **Boundaries**: - Tip of coccyx. - Ischial tuberosities. - Inferior border of pubic symphysis. - **Importance**: Exit point for the fetus during delivery. - **Pelvic Types**: - **Gynecoid**: Typical female pelvis; wide and shallow; favorable for vaginal delivery. - **Android**: Resembles male pelvis; narrow; may pose challenges during childbirth. - **Anthropoid**: Oval shape; adequate for delivery. - **Platypelloid**: Flat shape; may complicate labor. - **Pelvic Ligaments**: - **Sacrospinous Ligament**: From sacrum to ischial spine. - **Sacrotuberous Ligament**: From sacrum to ischial tuberosity. - **Function**: Stabilize pelvis; landmarks for anesthetic blocks. - **Pelvic Diameters**: - **Anteroposterior Diameter**: Distance from sacral promontory to pubic symphysis. - **Transverse Diameter**: Widest distance across pelvic inlet. - **Obstetric Conjugate**: Narrowest fixed distance the fetus must pass through; measured from sacral promontory to thickest part of pubic symphysis. **36. Roles of hCG, Progesterone, and Estradiol in Maintaining Early Pregnancy** - **Human Chorionic Gonadotropin (hCG)**: - **Source**: Secreted by syncytiotrophoblasts of the developing placenta. - **Functions**: - Maintains corpus luteum during early pregnancy, ensuring continued progesterone production. - Stimulates progesterone and estrogen secretion until the placenta takes over hormone production. - Basis for pregnancy tests due to its early presence in maternal blood and urine. - **Progesterone**: - **Source**: - Early Pregnancy: Corpus luteum. - Later Pregnancy: Placenta. - **Functions**: - Maintains endometrial lining for implantation. - Inhibits uterine contractions to prevent premature labor. - Modulates maternal immune response to allow tolerance of the fetus. - Stimulates development of mammary glands. - **Estradiol (Estrogen)**: - **Source**: - Early Pregnancy: Corpus luteum. - Later Pregnancy: Placenta (mainly estriol). - **Functions**: - Promotes uterine growth and blood flow. - Stimulates development of fetal organs. - Enhances myometrial sensitivity to oxytocin near term. - Increases expression of progesterone receptors in the uterus. **37. Characteristics and Actions of Oxytocin and Prolactin** - **Oxytocin**: - **Source**: Produced in hypothalamus; stored and released by posterior pituitary. - **Characteristics**: - Peptide hormone. - Short half-life (\~3-5 minutes). - **Actions**: - **Labor**: - Stimulates uterine contractions by acting on myometrial cells. - Positive feedback mechanism during childbirth; contractions increase oxytocin release. - **Lactation**: - Triggers milk ejection (\"let-down\" reflex) by causing contraction of myoepithelial cells in mammary glands. - **Behavioral Effects**: - Promotes bonding and social behaviors. - **Prolactin**: - **Source**: Secreted by lactotrophs in the anterior pituitary. - **Characteristics**: - Protein hormone. - Regulated by dopamine (inhibits prolactin secretion). - **Actions**: - **Lactation**: - Stimulates milk production in mammary glands. - Levels increase during pregnancy but milk production is inhibited by high estrogen and progesterone; after birth, decreased estrogen and progesterone allow prolactin to initiate lactation. - **Reproductive Effects**: - Inhibits GnRH secretion, leading to decreased FSH and LH; contributes to natural infertility during breastfeeding (lactational amenorrhea). **38. Components of the Urinary System and Their Functions** - **Kidneys**: - **Function**: Filter blood to remove waste products; regulate electrolyte balance, blood pressure, and red blood cell production. - **Structure**: Composed of cortex and medulla containing nephrons. - **Ureters**: - **Function**: Transport urine from kidneys to urinary bladder. - **Structure**: Muscular tubes with peristaltic movements. - **Urinary Bladder**: - **Function**: Stores urine until micturition. - **Structure**: - Detrusor muscle: Smooth muscle layer. - Trigone: Triangular area between ureteral orifices and urethral opening. - **Urethra**: - **Function**: Conveys urine from bladder to exterior. - **Differences**: - **Male**: Longer; also transports semen. - **Female**: Shorter; increased susceptibility to urinary tract infections. **39. Surface Anatomy and Anatomical Relationships of the Kidneys, Ureters, and Urinary Bladder** - **Kidneys**: - **Location**: - Retroperitoneal, on posterior abdominal wall. - Extend from T12 to L3 vertebrae. - Right kidney slightly lower due to liver. - **Surface Anatomy**: - Hilum located at L1-L2 level. - Protected by 11th and 12th ribs posteriorly. - **Anatomical Relationships**: - **Anterior to Right Kidney**: - Liver, duodenum, ascending colon. - **Anterior to Left Kidney**: - Stomach, spleen, pancreas, descending colon. - **Ureters**: - **Course**: - Descend retroperitoneally along psoas major muscle. - Cross over iliac vessels at pelvic brim. - Enter bladder at its posterior aspect. - **Constrictions** (sites of potential obstruction): - Ureteropelvic junction. - Crossing over iliac vessels. - Ureterovesical junction. - **Urinary Bladder**: - **Location**: - In the pelvic cavity, posterior to pubic symphysis. - In males: Anterior to rectum, superior to prostate gland. - In females: Anterior to uterus and vagina. - **Surface Anatomy**: - Can be palpated above pubic symphysis when full. **40. Major Blood Vessels and Path of Blood Flow Through the Kidney** - **Renal Arteries**: - **Origin**: Branches of abdominal aorta at L1-L2 level. - **Segmental Branches**: - **Anterior Branch**: Supplies anterior segments. - **Posterior Branch**: Supplies posterior segment. - **Path of Blood Flow**: - **Renal Artery** → - **Segmental Arteries** → - **Interlobar Arteries** (between pyramids) → - **Arcuate Arteries** (arch over base of pyramids) → - **Interlobular Arteries** (into cortex) → - **Afferent Arterioles** → - **Glomerular Capillaries** (site of filtration) → - **Efferent Arterioles** → - **Peritubular Capillaries** (in cortical nephrons) or - **Vasa Recta** (in juxtamedullary nephrons) → - **Venous Drainage**: - **Interlobular Veins** → - **Arcuate Veins** → - **Interlobar Veins** → - **Renal Vein** → - **Inferior Vena Cava** - **Renal Veins**: - **Left Renal Vein**: Longer; crosses anterior to aorta, receives left gonadal vein. - **Right Renal Vein**: Shorter; directly into IVC. **41. Nerve Supply to the Urinary System and Its Clinical Implications** - **Sympathetic Innervation**: - **Origin**: T10-L2 spinal segments. - **Pathways**: - **Renal Plexus**: Nerves reach kidneys along renal arteries. - **Effects**: - Vasoconstriction of renal blood vessels. - Modulation of urine formation. - Pain sensation from kidneys (referred to T10-L2 dermatomes). - **Parasympathetic Innervation**: - **Kidneys and Ureters**: Minimal parasympathetic supply. - **Bladder**: - **Pelvic Splanchnic Nerves (S2-S4)**: Stimulate detrusor muscle contraction and internal urethral sphincter relaxation during micturition. - **Sensory Innervation**: - **Visceral Afferent Fibers**: - Travel with sympathetic nerves for pain sensations. - Referred Pain: - **Kidney Pain**: Flank and back regions (T10-T12 dermatomes). - **Ureteral Pain**: Radiates from flank to groin (L1-L2 dermatomes). - **Micturition Reflex**: - **Process**: - Stretch receptors in bladder wall detect filling. - Afferent signals to spinal cord (S2-S4). - Efferent parasympathetic signals cause detrusor contraction and sphincter relaxation. - Voluntary control via pudendal nerve allows conscious regulation. **42. Development of the Urinary System and Common Developmental Abnormalities** - **Developmental Stages**: - **Pronephros**: Nonfunctional; degenerates early. - **Mesonephros**: Temporarily functional; contributes to reproductive ducts. - **Metanephros**: Becomes the permanent kidney. - **Formation of Metanephric Kidney**: - **Ureteric Bud**: - Outgrowth from mesonephric duct. - Forms ureter, renal pelvis, calyces, and collecting ducts. - **Metanephric Blastema**: - Mesenchymal tissue that forms nephrons (glomeruli, proximal and distal tubules, loop of Henle). - **Ascent of Kidneys**: - Initially located in pelvis; ascend to lumbar region due to differential growth. - **Common Developmental Abnormalities**: - **Horseshoe Kidney**: - Fusion of lower poles; ascent halted by inferior mesenteric artery. - **Renal Agenesis**: - Failure of ureteric bud and metanephric blastema interaction. - **Duplicated Ureter**: - Early splitting of ureteric bud. - **Ectopic Kidney**: - Failure to ascend; remains in pelvis. **43. Functions of the Kidneys** - **Excretory Functions**: - Removal of metabolic waste products (urea, creatinine). - Excretion of toxins and drugs. - **Regulatory Functions**: - **Electrolyte Balance**: Sodium, potassium, calcium, magnesium, chloride. - **Fluid Balance**: Regulation of extracellular fluid volume. - **Acid-Base Balance**: Reabsorption of bicarbonate; excretion of hydrogen ions. - **Endocrine Functions**: - **Renin Production**: Regulates blood pressure via RAAS. - **Erythropoietin**: Stimulates red blood cell production in response to hypoxia. - **Activation of Vitamin D**: Converts 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D (calcitriol), essential for calcium absorption. - **Blood Pressure Regulation**: - Through volume control and RAAS. - **Gluconeogenesis**: - Production of glucose from non-carbohydrate sources during prolonged fasting. **44. Structure and Function of a Nephron; Types of Nephrons** - **Nephron Components**: - **Glomerulus**: Network of capillaries where filtration occurs. - **Bowman\'s Capsule**: Encases glomerulus; collects filtrate. - **Proximal Convoluted Tubule (PCT)**: - Reabsorbs \~65% of filtered load (glucose, amino acids, sodium, water). - **Loop of Henle**: - **Descending Limb**: Permeable to water; concentrates filtrate. - **Ascending Limb**: Impermeable to water; actively reabsorbs Na+, K+, Cl-. - **Distal Convoluted Tubule (DCT)**: - Further Na+ and water reabsorption; regulated by aldosterone. - **Collecting Duct**: - Final concentration of urine; responsive to ADH (vasopressin). - **Types of Nephrons**: - **Cortical Nephrons**: - Located primarily in cortex. - Short loops of Henle. - Majority (\~85% of nephrons). - **Juxtamedullary Nephrons**: - Glomeruli near corticomedullary junction. - Long loops of Henle extending deep into medulla. - Important for urine concentration. **45. Movement of Solutes Through the Nephron** - **Filtration**: - Occurs at glomerulus. - Filters water and small solutes; excludes proteins and cells. - **Reabsorption**: - **PCT**: - Reabsorbs glucose, amino acids, bicarbonate, sodium, chloride, and water. - **Loop of Henle**: - **Descending Limb**: Water reabsorption. - **Ascending Limb**: Active reabsorption of Na+, K+, Cl-; impermeable to water. - **DCT and Collecting Duct**: - Fine-tuning of sodium and water reabsorption. - **Aldosterone**: Increases Na+ reabsorption and K+ secretion. - **ADH**: Increases water permeability in collecting duct. - **Secretion**: - **PCT**: - Secretes organic acids and bases (e.g., creatinine, drugs). - **DCT and Collecting Duct**: - Secrete K+ and H+ ions. - **Excretion**: - Final urine composition; substances not reabsorbed are excreted. **46. Structure and Features of the Glomerular Filtration Barrier** - **Components**: - **Fenestrated Endothelium**: - Pores (\~70-100 nm) allow passage of plasma but block cells. - **Glomerular Basement Membrane (GBM)**: - Thick, negatively charged matrix; repels proteins (e.g., albumin). - Composed of type IV collagen and proteoglycans. - **Podocytes**: - Epithelial cells with foot processes (pedicels). - **Slit Diaphragms**: Spaces between foot processes; further filtration barrier. - **Function**: - Selective permeability allows passage of water and small solutes. - Prevents filtration of large proteins and blood cells. - **Clinical Relevance**: - Damage to any component can lead to proteinuria or hematuria (e.g., in glomerulonephritis). **47. Production of Glomerular Filtrate and Its Composition** - **Mechanism**: - **Hydrostatic Pressure** in glomerular capillaries forces plasma through the filtration barrier into Bowman\'s space. - **Net Filtration Pressure**: - Determined by balance of hydrostatic and oncotic pressures in glomerular capillaries and Bowman\'s capsule. - **Composition of Filtrate**: - Similar to plasma but without significant proteins. - Contains water, electrolytes (Na+, K+, Cl-, HCO3-), glucose, amino acids, urea, and creatinine. **48. Factors Affecting Glomerular Filtration Rate (GFR)** - **Hydrostatic Pressure**: - **Glomerular Capillary Pressure**: Main driving force; increased by systemic blood pressure. - **Bowman\'s Capsule Pressure**: Opposes filtration; increased by urinary tract obstruction. - **Oncotic Pressure**: - **Plasma Oncotic Pressure**: Opposes filtration; increased by dehydration. - **Filtration Coefficient (Kf)**: - Depends on permeability and surface area of filtration barrier. - Decreased by damage or thickening of GBM. - **Regulation of GFR**: - **Autoregulation**: Maintains stable GFR over a range of blood pressures. - **Myogenic Mechanism**: Afferent arteriole constricts/dilates in response to pressure changes. - **Tubuloglomerular Feedback**: Macula densa senses NaCl; adjusts afferent arteriole tone. - **Pathological Factors**: - **Hypotension**: Decreases GFR. - **Hypertension**: Can damage glomeruli over time. - **Obstruction**: Increases Bowman\'s capsule pressure. **49. Regulation of GFR by Autoregulatory Feedback, Hormones, and Autonomic Neurons** - **Autoregulation**: - **Myogenic Mechanism**: Vascular smooth muscle responds to stretch. - **Tubuloglomerular Feedback**: - **Macula Densa Cells**: Detect increased NaCl delivery; release adenosine causing afferent arteriole constriction, reducing GFR. - **Juxtaglomerular Cells**: Release renin when perfusion pressure is low. - **Hormonal Regulation**: - **Renin-Angiotensin-Aldosterone System (RAAS)**: - **Angiotensin II**: Constricts efferent arteriole, maintaining GFR during low blood pressure. - **Atrial Natriuretic Peptide (ANP)**: - Released from atria in response to increased blood volume. - Dilates afferent arteriole; constricts efferent arteriole; increases GFR. - **Prostaglandins**: - Vasodilate afferent arteriole; counteract excessive vasoconstriction. - **Autonomic Regulation**: - **Sympathetic Nervous System**: - In response to stress or blood loss. - Vasoconstricts afferent arteriole; reduces GFR to conserve fluids. - Stimulates renin release. **50. Common Clinical Manifestations of Diseases Affecting the Glomerulus** - **Proteinuria**: - Excess protein in urine due to increased glomerular permeability. - Seen in nephrotic syndrome (e.g., minimal change disease, membranous nephropathy). - **Hematuria**: - Presence of blood in urine. - Indicative of glomerular damage (e.g., glomerulonephritis). - **Reduced GFR**: - Leads to accumulation of waste products (azotemia). - Symptoms include fatigue, nausea, and fluid overload. - **Edema**: - Due to hypoalbuminemia from protein loss. - Decreased oncotic pressure leads to fluid shift into interstitial spaces. - **Hypertension**: - Due to salt and water retention. - Can further damage glomeruli. - **Oliguria**: - Decreased urine output. - May indicate severe glomerular damage. **51. Transformation of Glomerular Filtrate into Urine via Tubular Reabsorption and Secretion** - **Tubular Reabsorption**: - **Purpose**: Recover essential substances from filtrate back into the bloodstream. - **Processes**: - **Active Transport**: Na+, glucose, amino acids. - **Passive Transport**: Water follows solutes osmotically. - **Sites**: - **PCT**: Major site of reabsorption. - **Loop of Henle**: Concentrates urine. - **DCT and Collecting Duct**: Regulated reabsorption. - **Tubular Secretion**: - **Purpose**: Eliminate additional wastes and regulate acid-base balance. - **Substances Secreted**: - H+, K+, NH4+, organic acids/bases, drugs. - **Sites**: - **PCT**: Secretion of organic compounds. - **DCT and Collecting Duct**: K+ and H+ secretion. - **Final Urine Formation**: - **Concentration and Dilution**: - Adjusted based on body\'s hydration status. - **ADH**: Increases water reabsorption in collecting ducts. **52. Principles Governing Tubular Reabsorption and Secretion** - **Active Transport**: - **Primary Active Transport**: Uses ATP directly (e.g., Na+/K+ ATPase). - **Secondary Active Transport**: Driven by ion gradients (e.g., glucose reabsorption via Na+-glucose co-transporter). - **Passive Transport**: - **Diffusion**: Movement along concentration gradients. - **Osmosis**: Water movement across semipermeable membranes. - **Transport Maximum (Tm)**: - Maximum rate at which a substance can be reabsorbed. - **Example**: Glucose Tm; exceeding this leads to glucosuria. - **Factors Influencing Secretion/Reabsorption**: - **Concentration Gradients**. - **Permeability of Tubule Segments**. - **Hormonal Control**: - **Aldosterone**: Increases Na+ reabsorption, K+ secretion. - **Parathyroid Hormone (PTH)**: Increases Ca2+ reabsorption, phosphate excretion. **53. Filtration, Reabsorption, Secretion, Excretion, and Renal Clearance** - **Definitions**: - **Filtration**: Movement of plasma from glomerulus to Bowman\'s capsule. - **Reabsorption**: Movement from tubular lumen back into peritubular capillaries. - **Secretion**: Movement from peritubular capillaries into tubular lumen. - **Excretion**: Elimination of substances in urine. - **Renal Clearance**: - **Concept**: Volume of plasma cleared of a substance per unit time. - **Formula**: - Clearance=Urine Concentration×Urine Flow RatePlasma Concentration\\text{Clearance} = \\frac{\\text{Urine Concentration} \\times \\text{Urine Flow Rate}}{\\text{Plasma Concentration}}Clearance=Plasma ConcentrationUrine Concentration×Urine Flow Rate​ - **Uses**: - **Inulin Clearance**: Measures GFR (freely filtered, neither reabsorbed nor secreted). - **PAH Clearance**: Measures renal plasma flow (completely secreted). **54. Kidneys in Regulating Water Balance** - **Mechanism**: - **Osmoreceptors** in hypothalamus detect plasma osmolarity. - **ADH Release**: - High osmolarity stimulates ADH secretion from posterior pituitary. - ADH increases water reabsorption in collecting ducts via insertion of aquaporin-2 channels. - **Thirst Mechanism**: - Stimulated by increased osmolarity; promotes water intake. - **Effect on Urine**: - **Dilute Urine**: Low ADH levels; collecting ducts impermeable to water. - **Concentrated Urine**: High ADH levels; water reabsorbed. **55. Role of the Countercurrent Mechanism in Urine Concentration** - **Countercurrent Multiplier**: - **Loop of Henle**: - Creates osmotic gradient in renal medulla. - **Descending Limb**: Permeable to water; water exits, filtrate becomes hyperosmotic. - **Ascending Limb**: Impermeable to water; active transport of Na+, K+, Cl- out of filtrate; filtrate becomes hypoosmotic. - **Countercurrent Exchanger**: - **Vasa Recta**: - Capillaries that parallel loop of Henle. - Preserve medullary gradient by exchanging solutes and water. - **Result**: - Allows kidneys to produce urine of varying concentration, conserving water when necessary. **56. Vasopressin (ADH) Regulation of Water Reabsorption** - **ADH Actions**: - Binds to V2 receptors on collecting duct cells. - Activates adenylate cyclase, increasing cAMP. - Promotes insertion of aquaporin-2 channels into apical membrane. - Increases water permeability; water reabsorbed into hyperosmotic medullary interstitium. - **Stimuli for ADH Release**: - **Increased Plasma Osmolarity**: Primary stimulus. - **Decreased Blood Volume/Blood Pressure**: Via baroreceptor signaling. - **Clinical Conditions**: - **Diabetes Insipidus**: - **Central**: Lack of ADH production. - **Nephrogenic**: Kidney unresponsive to ADH. **57. Kidneys in Sodium and Potassium Balance** - **Sodium Balance**: - **Reabsorption Sites**: - **PCT**: Majority (\~65%). - **Loop of Henle**: \~25%. - **DCT and Collecting Duct**: Fine-tuned regulation. - **Regulation**: - **Aldosterone**: - Increases Na+ reabsorption in DCT and collecting duct. - Promotes expression of ENaC channels and Na+/K+ ATPase. - **ANP**: - Inhibits Na+ reabsorption; promotes natriuresis. - **Potassium Balance**: - **Reabsorption**: - **PCT**: \~65%. - **Loop of Henle**: \~20%. - **Secretion**: - **Principal Cells in Collecting Duct**: Secrete K+ in exchange for Na+. - **Regulation**: - **Aldosterone**: Increases K+ secretion. - **Plasma K+ Levels**: High levels stimulate aldosterone release. **58. Renin-Angiotensin-Aldosterone System (RAAS) in Blood Pressure and Osmolarity** - **Activation**: - Triggered by low blood pressure, decreased NaCl delivery to macula densa, or sympathetic stimulation. - **Steps**: - - - - **Actions of Angiotensin II**: - Vasoconstricts arterioles, increasing blood pressure. - Stimulates aldosterone secretion from adrenal cortex. - Promotes Na+ and water reabsorption, increasing blood volume. - Stimulates ADH release and thirst. **59. Role of Kidneys in Acid-Base Balance** - **Mechanisms**: - **Reabsorption of Bicarbonate (HCO3-)**: - Mainly in PCT. - Carbonic anhydrase facilitates conversion of H+ and HCO3- to CO2 and H2O. - **Secretion of Hydrogen Ions (H+)**: - In DCT and collecting duct via intercalated cells. - **Type A Intercalated Cells**: Secrete H+ and reabsorb HCO3-. - **Generation of New Bicarbonate**: - Through metabolism of glutamine to produce NH4+ and HCO3-. - **Regulation**: - **Acidosis**: Increases H+ secretion and HCO3- reabsorption. - **Alkalosis**: Decreases H+ secretion; Type B intercalated cells secrete HCO3-. **60. Regulatory Mechanisms for Hydrogen Ion Transport in the Nephron** - **Proximal Tubule**: - **Na+/H+ Exchanger**: Secretes H+ in exchange for Na+. - **Reabsorption of Filtered HCO3-**. - **Thick Ascending Limb**: - **Similar Mechanisms**: Contribute to H+ secretion. - **Distal Tubule and Collecting Duct**: - **Intercalated Cells**: - **Type A**: Active during acidosis; secrete H+ via H+-ATPase and H+/K+-ATPase. - **Type B**: Active during alkalosis; secrete HCO3- and reabsorb H+. - **Buffers in Urine**: - **Phosphate Buffer System**: H+ combines with HPO4\^2- to form H2PO4\^-. - **Ammonia Buffer System**: NH3 combines with H+ to form NH4+. **61. Kidneys Producing Bicarbonate and Its Role in Acid-Base Balance** - **Generation of New HCO3-**: - **Ammoniagenesis**: - In PCT, glutamine is metabolized to NH4+ and HCO3-. - NH4+ is excreted; HCO3- is added to blood. - **Reabsorption of Filtered HCO3-**: - Prevents loss of bicarbonate in urine. - **Role in Acid-Base Balance**: - Maintains plasma HCO3- levels. - Compensates for metabolic acidosis by increasing HCO3- production. **62. Body\'s Defense Mechanisms Against Acid-Base Imbalances** - **Buffer Systems**: - **Bicarbonate Buffer System**: Immediate response. - **Phosphate Buffer System**: Important in intracellular fluids. - **Protein Buffers**: Hemoglobin in RBCs. - **Respiratory Compensation**: - Adjusting ventilation to alter CO2 (and thus H+) levels. - **Acidosis**: Increased ventilation to expel CO2. - **Alkalosis**: Decreased ventilation to retain CO2. - **Renal Compensation**: - Adjusting H+ secretion and HCO3- reabsorption. - Slower response but more effective long-term. - **Cellular Ion Exchange**: - H+/K+ exchange across cell membranes. **63. Mechanisms of Action of Drugs Acting in the RAAS and Clinical Use** - **ACE Inhibitors (e.g., Lisinopril)**: - **Mechanism**: Inhibit ACE, reducing angiotensin II production. - **Effects**: - Vasodilation. - Decreased aldosterone secretion. - Reduced blood pressure. - **Clinical Use**: Hypertension, heart failure, post-MI, diabetic nephropathy. - **Angiotensin II Receptor Blockers (ARBs) (e.g., Losartan)**: - **Mechanism**: Block AT1 receptors, preventing angiotensin II action. - **Effects**: Similar to ACE inhibitors. - **Clinical Use**: Alternative for patients intolerant to ACE inhibitors. - **Direct Renin Inhibitors (e.g., Aliskiren)**: - **Mechanism**: Inhibit renin activity, reducing angiotensin I and II. - **Clinical Use**: Hypertension. - **Aldosterone Antagonists (e.g., Spironolactone)**: - **Mechanism**: Block aldosterone receptors in collecting duct. - **Effects**: - Decrease Na+ reabsorption and K+ secretion. - Mild diuretic effect. - **Clinical Use**: Heart failure, hypertension, hyperaldosteronism. **64. Contraindications, Interactions, and Adverse Effects of RAAS Medications** - **ACE Inhibitors**: - **Contraindications**: - Pregnancy (teratogenic). - Bilateral renal artery stenosis. - **Adverse Effects**: - Dry cough (due to bradykinin accumulation). - Angioedema. - Hyperkalemia. - Hypotension. - **Interactions**: - Potassium-sparing diuretics (increase risk of hyperkalemia). - NSAIDs (reduce antihypertensive effect). - **ARBs**: - **Contraindications**: - Pregnancy. - **Adverse Effects**: - Hyperkalemia. - Dizziness. - **Interactions**: - Similar to ACE inhibitors but less risk of cough and angioedema. - **Aldosterone Antagonists**: - **Contraindications**: - Hyperkalemia. - Severe renal impairment. - **Adverse Effects**: - Hyperkalemia. - Gynecomastia (spironolactone). - **Interactions**: - ACE inhibitors/ARBs (increase hyperkalemia risk). **65. Causes and Consequences of Acute Kidney Injury (AKI)** - **Causes**: - **Prerenal AKI**: - Due to decreased perfusion (hypovolemia, hypotension, heart failure). - **Intrinsic AKI**: - **Acute Tubular Necrosis**: Ischemia or toxins damaging tubular cells. - **Glomerulonephritis**: Inflammation of glomeruli. - **Acute Interstitial Nephritis**: Allergic reaction affecting interstitium. - **Postrenal AKI**: - Obstruction of urinary outflow (stones, tumors, prostate enlargement). - **Consequences**: - **Azotemia**: Accumulation of nitrogenous wastes. - **Electrolyte Imbalances**: - Hyperkalemia (risk of cardiac arrhythmias). - Metabolic acidosis. - **Fluid Overload**: Edema, hypertension. - **Uremia**: Symptoms due to toxin accumulation (nausea, confusion). - **Management**: - Address underlying cause. - Supportive care (fluid management, electrolyte correction). - Dialysis if severe. **66. Why Chronic Kidney Disease (CKD) Affects Multiple Body Systems** - **Progressive Loss of Nephron Function**: - Decreased GFR over time. - **Systemic Effects**: - **Cardiovascular**: - Hypertension due to fluid overload. - Accelerated atherosclerosis. - Heart failure. - **Hematological**: - Anemia (decreased erythropoietin). - Bleeding tendencies (platelet dysfunction). - **Skeletal**: - Renal osteodystrophy (secondary hyperparathyroidism due to hypocalcemia and phosphate retention). - **Neurological**: - Peripheral neuropathy. - Encephalopathy. - **Gastrointestinal**: - Nausea, vomiting, anorexia. - **Endocrine/Metabolic**: - Insulin resistance. - Dyslipidemia. - **Immune System**: - Increased susceptibility to infections. - **Management**: - Slowing progression (blood pressure control). - Managing complications. - Preparation for renal replacement therapy. **67. Principles of Renal Replacement Therapy** - **Indications**: - End-stage renal disease (ESRD). - Severe AKI not responsive to conservative treatment. - **Modalities**: - **Hemodialysis**: - Blood passed through dialyzer with semipermeable membrane. - Removes waste products and excess fluid. - Requires vascular access (AV fistula). - **Peritoneal Dialysis**: - Dialysis fluid introduced into peritoneal cavity. - Peritoneal membrane acts as the filter. - Can be done at home. - **Renal Transplantation**: - Replacement of diseased kidney with donor kidney. - Requires immunosuppression. - **Principles**: - **Diffusion**: Movement of solutes from high to low concentration. - **Ultrafiltration**: Removal of fluid based on pressure gradients. - **Convection**: Solutes dragged along with water movement. **68. Mechanisms of Action of Diuretics and Their Clinical Use** - **Loop Diuretics (e.g., Furosemide)**: - **Site of Action**: Thick ascending limb of loop of Henle. - **Mechanism**: Inhibit Na+-K+-2Cl- co-transporter. - **Effects**: Powerful diuresis; increase excretion of Na+, Cl-, K+, Ca2+, Mg2+. - **Clinical Use**: Edema, heart failure, hypertension, hypercalcemia. - **Thiazide Diuretics (e.g., Hydrochlorothiazide)**: - **Site of Action**: Early distal convoluted tubule. - **Mechanism**: Inhibit Na+-Cl- co-transporter. - **Effects**: Moderate diuresis; increase excretion of Na+, Cl-, K+; reduce calcium excretion. - **Clinical Use**: Hypertension, mild edema, nephrolithiasis due to hypercalciuria. - **Potassium-Sparing Diuretics**: - **Aldosterone Antagonists (e.g., Spironolactone)**: - **Site**: Collecting duct. - **Mechanism**: Inhibit aldosterone receptors. - **Clinical Use**: Heart failure, hyperaldosteronism. - **ENaC Inhibitors (e.g., Amiloride)**: - **Mechanism**: Block epithelial Na+ channels. - **Clinical Use**: Often combined with other diuretics to prevent hypokalemia. - **Osmotic Diuretics (e.g., Mannitol)**: - **Site**: Proximal tubule and descending limb. - **Mechanism**: Increase osmolarity of filtrate, preventing water reabsorption. - **Clinical Use**: Reduce intracranial or intraocular pressure. - **Carbonic Anhydrase Inhibitors (e.g., Acetazolamide)**: - **Site**: Proximal tubule. - **Mechanism**: Inhibit carbonic anhydrase, reducing HCO3- reabsorption. - **Clinical Use**: Glaucoma, altitude sickness, metabolic alkalosis. **69. Contraindications, Interactions, and Adverse Effects of Diuretics** - **Loop Diuretics**: - **Adverse Effects**: - Hypokalemia, hypocalcemia, ototoxicity, dehydration. - **Contraindications**: - Severe electrolyte depletion. - **Interactions**: - Aminoglycosides (increased ototoxicity). - NSAIDs reduce efficacy. - **Thiazide Diuretics**: - **Adverse Effects**: - Hypokalemia, hyponatremia, hypercalcemia, hyperuricemia (gout), hyperglycemia. - **Contraindications**: - Anuria, hypersensitivity to sulfonamides. - **Interactions**: - Lithium (increased toxicity), NSAIDs. - **Potassium-Sparing Diuretics**: - **Adverse Effects**: - Hyperkalemia, gynecomastia (spironolactone). - **Contraindications**: - Hyperkalemia, renal failure. - **Interactions**: - ACE inhibitors, ARBs (increase risk of hyperkalemia). - **Osmotic Diuretics**: - **Adverse Effects**: - Dehydration, electrolyte imbalances. - **Contraindications**: - Anuria, severe dehydration, pulmonary edema. - **Carbonic Anhydrase Inhibitors**: - **Adverse Effects**: - Metabolic acidosis, kidney stones, hypokalemia. - **Contraindications**: - Cirrhosis, severe renal impairment.