Acid-Base Balance and Mineral Regulation

Acid-Base Balance

• The body's normal pH is 7.35-7.45, maintained by regulating bicarbonate or excreted H+
• Major organs involved in regulation are bones, lungs, and kidneys
• Death occurs outside of the pH range of 6.8 to 7.8

Regulation of Acid-Base Balance

• Respiratory system: regulated by the lungs, focuses on CO2 (carbon dioxide)
• Metabolic system: regulated by the kidneys, focuses on HCO3− (bicarbonate)
• Equation: CO2 + H2O ↔ H2CO3 ↔ HCO3− + H+
  • ↑ in CO2 creates carbonic acid, producing H+

Metabolic Acidosis

• Causes: increased acid production, decreased bicarbonate production/elimination
  • Increased acid production: diabetic ketoacidosis, lactic acidosis, alcoholic ketoacidosis
  • Decreased bicarbonate production/elimination: renal failure, diarrhea
• Manifestations: Kussmaul respirations, lethargy, confusion, coma
• Treatment: sodium bicarbonate, fluids, treat underlying cause

Metabolic Alkalosis

• Causes: excessive loss of metabolic acids (e.g., chloride), increased bicarbonate intake
  • Excessive loss of metabolic acids: vomiting, diuretics, hypokalemia, prolonged nasogastric suctioning
  • Increased bicarbonate intake: ingestion of large amounts of baking soda
• Treatment: Sodium chloride, potassium, and chloride IV (chloride replaces bicarbonate)

Respiratory Acidosis

• Causes: alveolar hypoventilation (decreased ventilation)
  • Alveolar hypoventilation: COPD, pneumonia, pulmonary edema, neuromuscular disorders
• Manifestations: dyspnea, headache, confusion, lethargy, coma
• Treatment: restore adequate ventilation, mechanical ventilation, oxygen therapy

Respiratory Alkalosis

• Causes: hyperventilation, decreased plasma CO2 (hypocapnia)
  • Hyperventilation: anxiety, pain, fever, high altitude, sepsis
• Manifestations: dizziness, lightheadedness, paresthesias, muscle cramps, tetany
• Treatment: paper bag, treat hypoxemia and hypermetabolic states

Calcium

• Ionized form has a range of 5.5-5.6 mg/dL
• Most calcium is found in bones as hydroxyapatite
• Necessary for:
  • Nerve impulse transmission
  • Muscle contraction
  • Blood clotting
  • Bone formation
  • Enzyme activation

Phosphate

• Serum levels: 2.5-4.5 mg/dL (adults)
• Most phosphate (85%) is located in bone
• Necessary for:
  • High-energy bonds in creatine phosphate and ATP
  • Anion buffer
  • Muscle contraction energy

Calcium and Phosphate Regulation

• Parathyroid hormone (PTH): increases calcium levels, decreases phosphate levels
• Vitamin D: increases both calcium and phosphate levels
• Calcitonin: decreases calcium levels, decreases phosphate levels

Hypocalcemia

• Calcium levels less than 10.5 mg/dL
• Causes: hypoparathyroidism, vitamin D deficiency, renal failure, pancreatitis, hypoalbuminemia
• Manifestations: tetany, muscle spasms, seizures, confusion

Hypophosphatemia

• Serum phosphate level less than 2.0 mg/dL
• Causes: intestinal malabsorption, renal excretion, vitamin D deficiency, antacid use, alcohol abuse, malabsorption syndromes
• Manifestations: diminished oxygen release, osteomalacia, muscle weakness, bleeding disorders, leukocyte alterations, rickets
• Treatment: treat underlying condition

Hyperphosphatemia

• Serum level greater than 4.7 mg/dL
• Causes: exogenous or endogenous addition of phosphate to ECF, chemotherapy, long-term use of phosphate enemas
• Manifestations: same as hypocalcemia with possible calcification of soft tissue
• Treatment: treat underlying condition, aluminum hydroxide, dialysis

Buffers

• Chemicals that bind excess H+ or OH- without a significant change in pH
• Located in ICF and ECF
• Consist of a buffering pair: weak acid and its conjugate base
• Most important plasma buffering systems: carbonic acid-bicarbonate system and hemoglobin

Carbonic Acid-Bicarbonate Buffering

• Operates in the lungs and kidneys
• ↑ partial pressure of carbon dioxide (pCO2) → ↑ carbonic acid formation
• Lungs: decrease carbonic acid by expelling CO2
• Kidneys: reabsorb or regenerate bicarbonate (slower reaction than lungs)
• Acidosis: bicarbonate decreases, lowering pH
• pH restoration: decrease carbonic acid to compensate
• Respiratory compensation: increasing/decreasing ventilation
• Renal compensation: producing acidic or alkaline urine

Other Buffering Systems

• Protein buffering: proteins act as buffers due to their amino acid structure
• Respiratory and renal buffering: interlinked systems to maintain pH
• Cellular ion exchange: cells exchange ions (e.g., H+ for potassium) to maintain internal pH

Anion Gap

• Measures the difference between negatively and positively charged electrolytes in the blood
• High gap: indicates blood is more acidic
• Low gap: indicates blood is less acidic

Magnesium

• Mostly stored in muscle and bone
• Interacts with calcium
• Plasma concentration of 1.5-3.0 mg/dL
• Cofactor in intracellular reactions, protein synthesis, nucleic acid stability, neuromuscular excitability

Hypomagnesemia

• Causes: malnutrition, alcoholism, diuretics, diarrhea
• Manifestations: muscle weakness, tremors, tetany, seizures, arrhythmias

Hypermagnesemia

• Causes: renal failure, excessive intake of magnesium-containing medications
• Manifestations: muscle weakness, fatigue, nausea, vomiting, hypotension, bradycardia

Sexual Abuse and Genetics

• Sexual abuse by a first-degree relative increases the risk of recessive genetic disorders.

Nondisjunction

• Failure of chromosomes to separate properly during meiosis
• Results in gametes with an abnormal number of chromosomes
• Can lead to aneuploidy (abnormal chromosome number)

Transcription

• Process of making mRNA from DNA
• Takes place in the nucleus
• Steps of Transcription:
  • Initiation: RNA polymerase binds to the promoter region of the DNA
  • Elongation: RNA polymerase reads the DNA template and synthesizes a complementary RNA molecule
  • Termination: RNA polymerase reaches the terminator sequence and detaches from the DNA

RNA

• RNA has uracil (U) instead of thymine (T)
• RNA is single-stranded, while DNA is double-stranded
• Types of RNA:
  • mRNA (messenger RNA): carries genetic information from DNA to ribosomes
  • tRNA (transfer RNA): carries amino acids to ribosomes
  • rRNA (ribosomal RNA): forms part of the ribosome

Down Syndrome

• Trisomy 21 (three copies of chromosome 21)

• Characteristics:

  • Upward slanting eyes
  • Flattened face
  • Single deep crease across palm of hand
  • Intellectual disability
  • Increased risk of heart defects, leukemia, and Alzheimer's disease

Sex Chromosome Aneuploidies

• Trisomy X: XXX; females with extra X chromosome
  • Symptoms: tall stature, infertility, learning disabilities
• Turner's syndrome: XO; females with only one X chromosome
  • Symptoms: short stature, webbed neck, broad chest, heart defects, infertility
• Klinefelter's syndrome: XXY; males with extra X chromosome
  • Symptoms: tall stature, small testes, gynecomastia (breast development), low testosterone levels, learning disabilities

Fragile X Syndrome

• **Second most common genetic cause of intellectual disability (after Down syndrome)
• Inheritance: X-linked dominant
  • Female carrier passes the gene to offspring
• Characteristics:
  • Intellectual disability
  • Large ears
  • Prominent forehead
  • Long face
  • Macroorchidism (enlarged testicles)

Expressivity

• Variation in the severity of a genetic disorder among individuals who have the same mutation
• Example: some individuals with cystic fibrosis may have severe lung disease, while others may have mild symptoms

Prader-Willi syndrome

• Deletion on chromosome 15
• Features:
  • Hypotonia
  • Obesity
  • Small hands and feet
  • Hypogonadism
  • Intellectual disability

Incidence Rate

• Number of new cases of a disease that occur in a population over a specific time period

Colorectal Cancer

• Factors:
  • Genetics
  • Environmental factors (dietary, lifestyle)
  • Age
  • Family history
• Screening:
  • Colonoscopy
  • Fecal occult blood test
  • Sigmoidoscopy

Methylation

• Addition of a methyl group (CH3) to a molecule.
• Impacts gene expression
• Can lead to:
  • Gene silencing: methylation can turn off gene expression
  • Gene activation: demethylation can turn on gene expression
• Role in Cancer:
  • Abnormal methylation patterns can contribute to cancer development

Sickle Cell Anemia

• Inherited blood disorder
• Mutation in the gene that codes for hemoglobin
• Red blood cells become sickle-shaped
• Symptoms:
  • Painful episodes (crises)
  • Fatigue
  • Jaundice
  • Delayed growth
• Treatment:
  • Pain management
  • Blood transfusions
  • Hydroxyurea

Autosomal Dominant vs Autosomal Recessive Disorders

• Similarity: Both occur on the 22 pairs of autosomes (not sex chromosomes)
• Autosomal Dominant:
  • Only one copy of the mutated gene is needed to develop the disorder
  • Example: Huntington disease, Marfan syndrome
• Autosomal Recessive:
  • Two copies of the mutated gene are needed to develop the disorder
  • Example: cystic fibrosis, sickle cell anemia

DNA Polymerase Function

• Enzyme involved in DNA replication
• Function:
  • Reads the template DNA strand
  • Adds complementary nucleotides to the new DNA strand

Familial Hypercholesterolemia (FH)

• Inherited disorder
• Mutation affects LDL receptor
• High levels of LDL (bad cholesterol)
• Increased risk of cardiovascular disease

Breast Cancer

• Leading type of cancer in women
• Risk factors:
  • Genetics
  • Family history
  • Age
  • Early menarche (first menstrual period)
  • Late menopause
  • Hormone replacement therapy
  • Obesity
  • Alcohol consumption
• Screening:
  • Mammography
  • Breast self-exam
  • MRI

IgE, IgM, and IgG

• Types of Antibodies:
  • IgE: involved in allergic reactions
  • IgM: first antibody produced during an immune response
  • IgG: most abundant antibody in the blood; provides long-term immunity

Staphylococcus

• Bacterium that is commonly found on the skin and in the nose.
• Causes: skin infections (e.g., boils, impetigo), wound infections
• Virulence factors:
  • Produces toxins that damage tissues
  • Forms biofilms that protect it from antibiotics

Acquired Immunodeficiency Syndrome (AIDS)

• Caused by the human immunodeficiency virus (HIV)
• HIV targets the CD4+ T cells
• Progression:
  • Initially, HIV replicates rapidly
  • Over time, CD4+ T cell count declines
  • Immune system weakens
  • Individuals become susceptible to opportunistic infections
• Symptoms:
  • Flu-like symptoms
  • Weight loss
  • Fatigue
  • Opportunistic infections

Benefits of a Fever

• Part of the body's natural defense system
• Helps fight infection:
  • Increases immune cell activity
  • Inhibits bacterial growth
• Other benefits:
  • Increases metabolism
  • Promotes tissue repair
  • Reduces the iron available to bacteria

Innate Immune Response

• First line of defense against infection
• Non-specific
• Immediate:
  • Physical and Mechanical Barriers:
    • Skin
    • Mucous membranes
    • Cilia
    • Coughing
    • Sneezing
  • Biochemical Barriers:
    • Antimicrobial substances (e.g., lysozyme, lactoferrin, interferon)
    • pH of body fluids
  • Normal Microbiome:
    • Compete with pathogens for nutrients
    • Produce antimicrobial substances
• Second line of defense:
  • Inflammation:
    • Body's response to tissue injury or infection
    • Signs:
      • Redness
      • Swelling
      • Heat
      • Pain
      • Loss of function
  • Phagocytosis:
    • Engulfment and destruction of pathogens by phagocytes (e.g., neutrophils, macrophages)
  • Natural Killer (NK) cells:
    • Destroy virus-infected cells and cancer cells

Primary Lymphoid Tissue Example

• Bone marrow
• Thymus

Type 1-4 Hypersensitivity Reactions

• Exaggerated immune response to a normally harmless antigen
• Types of hypersensitivity:
  • Type 1 (Immediate):
    • IgE-mediated
    • Example: anaphylaxis, allergic rhinitis, asthma
  • Type 2 (Cytotoxic):
    • IgG or IgM-mediated
    • Destruction of cells by antibody and complement
    • Example: hemolytic anemia, transfusion reactions
  • Type 3 (Immune Complex):
    • Immune complexes form and deposit in tissues
    • Trigger inflammation and tissue damage
    • Example: systemic lupus erythematosus (SLE), rheumatoid arthritis
  • Type 4 (Delayed):
    • T cell-mediated
    • Delayed response (24-48 hours)
    • Example: contact dermatitis, tuberculin reaction

Endotoxins and Exotoxins

• Endotoxins:
  • Component of the outer membrane of gram-negative bacteria
  • Released when bacteria die
  • Can trigger a strong immune response and inflammation
• Exotoxins:
  • Proteins produced by both gram-positive and gram-negative bacteria
  • Released by living bacteria
  • Can have specific toxic effects on target cells

Acute Bacterial Meningitis - Lab Findings

• Elevated white blood cell count (WBC)
• Elevated protein levels in cerebrospinal fluid (CSF)
• Decreased glucose levels in CSF

Severe Neutropenia - Isolation Rationale

• Patient is at high risk for infection because of low neutrophil count
• Neutrophils are essential for fighting bacterial infections
• Isolation helps prevent the patient from contracting infections

Alloimmunity

• Immune response directed against antigens from a different individual of the same species
• Example:
  • Transfusion reaction: recipient's immune system attacks donor's red blood cells

Acute Inflammation - Line of Defense

• Second line of defense
• Non-specific
• Vascular Response:
  • Vasodilation
  • Increased vascular permeability
• Cellular Response:
  • Neutrophil and macrophage activation
  • Phagocytosis
• Chemical mediators:
  • Histamine, prostaglandins, cytokines

Systemic Lupus Erythematosus (SLE)

• Chronic autoimmune disease
• Characterized by the production of autoantibodies against a variety of self-antigens
• Clinical features:
  • Joint pain
  • Fatigue
  • Skin rashes
  • Kidney inflammation (nephritis)
  • Neurological problems

MHC Facts

• Major Histocompatibility Complex (MHC):
  • Set of genes that code for cell surface proteins
  • Function: present antigens to T cells
  • Types of MHC molecules:
    • MHC class I: expressed on all nucleated cells
    • MHC class II: expressed on antigen-presenting cells (APCs)

Humoral Immunity

• Antibody-mediated immunity
• B cells are the primary cells

Adaptive Immunity

• Specific
• Acquired through exposure to antigens
• Components:
  • Humoral immunity: antibody-mediated
  • Cell-mediated immunity: T cell-mediated

Humoral Immunity

• Mechanism:
  • B cells differentiate into plasma cells, which produce antibodies (immunoglobulins)
  • Antibodies bind to specific antigens and neutralize them, leading to their destruction
• Functions:
  • Neutralize toxins and viruses
  • Opsonize bacteria (make them more susceptible to phagocytosis)
  • Activate complement (a set of proteins that contribute to inflammation and cell lysis)

Cell-mediated Immunity

• Mechanism:
  • T cells recognize and destroy infected cells, tumor cells, or cells that express foreign antigens
  • Types of T cells:
    • Cytotoxic T cells (CD8+): directly kill target cells
    • Helper T cells (CD4+): activate other immune cells
• Functions:
  • Destroy infected cells
  • Eliminate cancer cells
  • Coordinate immune responses

Innate Immune System: PAMPs and DAMPs

• Pathogen-associated molecular patterns (PAMPs):
  • Molecules that are characteristic of pathogens (e.g., lipopolysaccharide [LPS] in gram-negative bacteria)
  • Recognized by pattern recognition receptors (PRRs) on innate immune cells
• Damage-associated molecular patterns (DAMPs):
  • Molecules released from damaged or stressed cells
  • Also recognized by PRRs
• Both PAMPs and DAMPs trigger innate immune responses

Dysfunctional Wound Healing

• Usually caused by infection
• Prolonged inflammation
• Failure of re-epithelialization
• Seen in autoimmune diseases: rheumatoid arthritis, lupus, scleroderma
• Treatment: Debridement, addressing underlying conditions

Innate Immunity

• First line of defense
• Non-specific
• Immediate
• Examples: skin, mucous membranes, neutrophils, macrophages

Metastasis

• Hallmark: development of secondary masses not directly connected to the originating tumor
• Features:
  • Ability to invade surrounding tissues
  • Ability to migrate to distant sites through blood or lymph
  • Ability to establish new tumors at distant sites

Reasons for Cancerous Growth

• Uncontrolled cell proliferation
• Evasion of apoptosis (programmed cell death)
• Ability to invade surrounding tissues
• Ability to metastasize to distant sites

Dysplasia

• Abnormal cell growth
• Not cancer, but it can sometimes become cancer
• Features:
  • Abnormal cell size, shape, and organization
  • Increased cell proliferation

Carcinoma in Situ

• Cancer cells confined to the epithelium
• Has not invaded surrounding tissues
• Early stage of cancer

Malignant Tumor

• Cancerous tumor
• Features:
  • Rapid growth
  • Ability to invade surrounding tissues
  • Ability to metastasize to distant sites

Malignant Tumor Facts

• Invasiveness: penetrate surrounding tissues and grow into adjacent structures
• Anaplasia: loss of differentiation and organization of cells
• Metastasis: spreading to distant sites through blood or lymphatic system
• Angiogenesis: formation of new blood vessels to support tumor growth
• Evading immune system: cancer cells develop mechanisms to avoid detection and destruction by immune cells
• Self-sufficiency: no longer need growth factors from the body to grow

Human Carcinogenesis - Key Genetic Mechanisms

• Mutations in oncogenes: genes that normally promote cell growth and proliferation
• Mutations in tumor suppressor genes: genes that normally inhibit cell growth and proliferation
• Epigenetic changes: alterations in gene expression without changes in the DNA sequence

Hallmarks of Cancer

• Sustained proliferative signaling: cancer cells continuously signal themselves to grow and divide
• Evading growth suppressors: cancer cells disable genes that normally stop cell growth
• Resisting cell death: cancer cells evade programmed cell death (apoptosis)
• Enabling replicative immortality: cancer cells activate the enzyme telomerase to maintain their chromosome ends during cell division
• Inducing angiogenesis: cancer cells promote the formation of new blood vessels to supply oxygen and nutrients
• Activating invasion and metastasis: cancer cells break through basement membranes and spread to distant sites
• Genome instability and mutation: cancer cells develop mutations that lead to more mutations
• Tumor-promoting inflammation: inflammation can promote the growth and spread of cancer

Describe Oncogene Capability

• Oncogenes are genes that promote cell growth and proliferation when they are mutated
• Activated oncogenes contribute to cancer development

Hematopoiesis

• Process of blood cell formation
• Occurs primarily in the bone marrow

HIV - Patient Risks

• Patients with HIV are at increased risk for:
  • Opportunistic infections: infections caused by organisms that normally do not cause disease in healthy individuals
  • Cancers: certain cancers, such as Kaposi's sarcoma, are more common in people with HIV

Macrocytic Normochromic Anemias

• Caused by:
  • Deficiency in vitamin B12 or folate
  • Impaired DNA synthesis
  • Large, immature red blood cells (macrocytes)

Non-Hodgkin's Lymphoma

• Cancer of the lymphatic system
• More common and aggressive than Hodgkin's lymphoma
• Types:
  • Burkitt lymphoma: fast-growing
  • Diffuse large B-cell lymphoma: most common type

TNM Staging

• TNM staging system:
  • T (tumor): describes the size and location of the primary tumor
  • N (nodes): describes the extent of spread to nearby lymph nodes
  • M (metastasis): describes whether the cancer has spread to distant sites

Viruses Linked to Cancer

• Epstein-Barr virus (EBV): associated with Burkitt lymphoma, Hodgkin's lymphoma, and nasopharyngeal carcinoma
• Human papillomavirus (HPV): associated with cervical cancer, anal cancer, and head and neck cancers
• Hepatitis B virus (HBV) and hepatitis C virus (HCV): associated with liver cancer
• Human T-cell leukemia virus type 1 (HTLV-1): associated with adult T-cell leukemia/lymphoma
• Human herpesvirus 8 (HHV-8): associated with Kaposi's sarcoma

Obesity Facts

• Obesity: a major risk factor for many chronic diseases, including cancer, type 2 diabetes, heart disease, and stroke
• Characterized by: excessive body fat

Granulocytes

• Type of white blood cells
• Contain granules in their cytoplasm
• Order of abundance (Never Let Monkeys Eat Bananas):
  • Neutrophils: most abundant; phagocytize bacteria
  • Lymphocytes: important for adaptive immunity
  • Monocytes: differentiate into macrophages; phagocytize pathogens
  • Eosinophils: involved in allergic reactions and parasitic infections
  • Basophils: release histamine and other inflammatory mediators

Anemia of Chronic Disease

• Caused by: inflammation, infection, and chronic diseases (e.g., cancer, rheumatoid arthritis, heart failure
• Pathophysiology:
  • Decreased production of red blood cells
  • Increased destruction of red blood cells
  • Iron deficiency (often but not always)

Sign of Splenic Sequestration After Sickle Cell Crisis

• Pain in the left upper abdomen
• Enlarged spleen
• Reduced blood flow to the spleen

How Cancer Cells Use Telomerase

• Telomeres: protective caps on the ends of chromosomes
• Telomerase: enzyme that adds DNA to the ends of chromosomes, preventing them from shortening during cell division
• Normal cells: telomerase activity is low
• Cancer cells: telomerase activity is often high
• Consequences: cancer cells can divide indefinitely, contributing to tumor growth

Monocytes Become

• Macrophages

ITP

• Immune Thrombocytopenic Purpura
• Autoimmune disorder
• Antibodies destroy platelets
• Symptoms:
  • Bleeding (e.g., nosebleeds, easy bruising)
  • Petechiae (tiny red spots)
• Treatment:
  • Corticosteroids
  • Immunoglobulin therapy
  • Splenectomy

TTP

• Thrombotic Thrombocytopenic Purpura
• Rare disorder
• Formation of microthrombi (small blood clots) in small blood vessels
• Symptoms:
  • Thrombocytopenia (low platelet count)
  • Microangiopathic hemolytic anemia (destruction of red blood cells)
  • Neurological problems (e.g., headache, confusion, seizures)
  • Renal failure
• Treatment:
  • Plasma exchange
  • Corticosteroids
  • Immunosuppressants

Contributors to Hemostasis

• Hemostasis: process of stopping bleeding
• Steps:
  • Constriction of blood vessels
  • Formation of a platelet plug
  • Coagulation (blood clotting)
• Contributors:
  • Platelets: small cell fragments that help form clots
  • Coagulation factors: proteins in the blood that participate in the clotting process
  • Blood vessels: play a role in vasoconstriction and providing the surface for clot formation

Iron Deficiency Anemia Lab Findings

• Low hemoglobin level
• Low hematocrit
• Low serum iron level
• Low serum ferritin level
• Increased total iron-binding capacity (TIBC)

Glandular Epithelial Malignancy Example

• Adenocarcinoma

Calcium Ions Role in Presynaptic Membrane

• Influx of calcium ions into the presynaptic terminal triggers the release of neurotransmitters into the synaptic cleft

Acute Otitis Media - Typical Presentation and Patho Findings

• Symptoms:
  • Earache
  • Fever
  • Irritability
  • Pulling at the ear
  • Fluid drainage from the ear
• Pathophysiology:
  • Inflammation and infection of the middle ear
  • Often caused by bacteria
  • Can be associated with Eustachian tube dysfunction

Cause of Global Cerebral Ischemia

• Complete cessation of blood flow
• Affects the entire brain

Cause of Focal Cerebral Ischemia

• Reduced blood flow to a specific area of the brain
• Often caused by a blood clot or other blockage in an artery

Temporal Arteritis - Giant Cell Arteritis

• Inflammation of the temporal artery
• Most common in people over 50 years old
• Symptoms:
  • Headache (often severe and located in the temples)
  • Tenderness and pain in the temporal artery
  • Jaw claudication (pain in the jaw when chewing)
  • Visual disturbances (e.g., blurred vision, double vision)
• Treatment:
  • Corticosteroids

Spinal Cord Injury - Dermatome Analysis

• Dermatome: area of skin whose sensory nerves all come from a single spinal nerve root
• Dermatome analysis:
  • Used to assess the level of spinal cord injury
  • Testing: applying light touch to specific areas of skin to determine which dermatomes are affected

Test your knowledge on acid-base balance and mineral regulation in the human body. This quiz covers pH levels, organ functions, and the hormones involved in maintaining the body's acid-base equilibrium and mineral levels. Challenge yourself with questions on metabolic alkalosis, calcium, and phosphate regulation.