PHYSIOLOGY THE CELL AND HOMEOSTASIS ANGELICA D FRANCISCO

PHYSIOLOGY: THE CELL AND HOMEOSTASIS ANGELICA D FRANCISCO, MD, MSC

OBJECTIVES REVIEW THE STRUCTURES OF THE CELL AND THEIR FUNCTION. 2. REVIEW THE HIERARCHY OF ORGANIZATION OF THE HUMAN BODY. 3. DEFINE THE “INTERNAL ENVIRONMENT” OF THE CELL. 4. EXPLAIN THE IMPORTANCE OF 1.

OBJECTIVES DEFINE HOMEOSTASIS. 6. DESCRIBE THE MECHANISM OF A NEGATIVE FEEDBACK SYSTEM. 7. EXPLAIN THE “GAIN” IN NEGATIVE FEEDBACK SYSTEMS. 5.

OBJECTIVES DESCRIBE THE MECHANISM OF POSITIVE FEEDBACK SYSTEM. 9. EXPLAIN HOW THE CHANGE IN POSITIVE FEEDBACK SYSTEM CAN BE USEFUL, AND POTENTIALLY HARMFUL. 8.

PHYSIOLOGY HUMAN PHYSIOLOGY Ø THE STUDY OF THE FUNCTION AND THE REGULATION OF THE DIFFERENT ORGAN SYSTEMS OF THE BODY COMPARATIVE PHYSIOLOGY CELLULAR & MOLECULAR PHYSIOLOGY

THE CELL Ø THE BASIC LIVING UNIT OF THE BODY

CELL ORGANELLES MEMBRANE-BOUND Ø Ø Ø Ø NUCLEUS PLASMA MEMBRANE MITOCHONDRIA ENDOPLASMIC RETICULUM GOLGI APPARATUS LYSOSOMES PEROXISOMES CYTOSKELETON MICROFILAMENTS (ACTIN FILAMENTS) Ø INTERMEDIATE FILAMENTS Ø MICROTUBULES Ø

NUCLEUS

CELL MEMBRANE FUNCTIONS 1. TRANSPORT OF SUBSTANCES 2. CELL RECOGNITION 3. CELL COMMUNICATION 4. TISSUE ORGANIZATION 5. ENZYMATIC ACTIVITY 6. CELL MORPHOLOGY

MITOCHONDRIA

MITOCHONDRIA & ATP

ATP & CELL METABOLISM

ENDOPLASMIC RETICULUM

ENDOPLASMIC RETICULUM ROUGH ER SMOOTH ER Ø PRESENCE OF RIBOSOMES Ø CELLS ACTIVE PROTEIN SYNTHESIS & SECRETION Ø FUNCTION Ø PROTEIN SYNTHESIS FUNCTION Ø SYNTHESIS OF FATS & LIPIDS Ø DETOXIFICATION OF SUBSTANCES Ø SEQUESTERS CA++ § TRANSLATION OF MRNA ABSENCE OF RIBOSOMES § SARCOPLASMIC RETICULUM

GOLGI APPARATUS

GOLGI APPARATUS FUNCTION ØPOST-TRANSLATIONAL MODIFICATION OF PROTEINS ØPACKAGES PROTEINS FOR DELIVERY

SECRETORY GRANULES

PROTEIN & LIPID SYNTHESIS

LYSOSOMES Ø CONTAINS DIGESTIVE ENZYMES FUNCTION Ø DEGRADATIVE FUNCTION § EG. MACROPHAGE

PHAGOCYTOSIS HTTP: //STUDENT. CCBCMD. EDU/COURSES/BIO 141/LECGUIDE/

PEROXISOMES Ø CONTAINS OXIDATIVE ENZYMES FUNCTION Ø OXIDIZE FATTY ACIDS Ø DETOXIFY COMPOUNDS § EG. LIVER CONVERSION OF ETHANOL TO ACETALDEHYDE

CYTOSKELETON FUNCTION ØMAINTAIN CELL STRUCTURE ØCHANGE CELL SHAPE ØCELL MOTILITY

CYTOSKELETON ACTIN MICROFILAMENTS ØLOCOMOTION ØLINK TO ADJACENT CELLS § ZONULA ADHERENS/OCCLUDENS INTERMEDIATE FILAMENTS ØINTRACELLULAR STRUCTURE § KERATIN IN EPITHELIAL CELLS

MICROTUBULES

MICROTUBULES FUNCTIONS ØINTRACELLULAR TRANSPORT OF VESICLES W/ MOTOR PROTEINS: KINESIN & DYNEIN ØCHROMOSOME MOVEMENT IN MITOSIS/ MEIOSIS ØMOVEMENT OF CILIA & FLAGELLA §

LYSOSOMAL DISEASES Ø ABSENCE OF LYSOSOMAL ENZYMES TAY-SACH’S DISEASE § HEXOSEAMINIDASE A § ACCUMULUATION OF GANGLIOSIDE IN NEURONS LORENZO’S OIL: ACCUMULATION OF VERY LONG CHAIN FATTY ACIDS, VLCFCAS

MICROTUBULES & CANCER Ø UNCONTROLLED MITOSIS IN TUMOR CELLS ANTITUMOR DRUGS Ø VINCRISTINE § PREVENTS FORMATION OF MICROTUBULES Ø TAXOL § STABILIZES MICROTUBULES

LEVELS OF ORGANIZATION DAVID SHIER, JACKIE BUTLER, RICKI LEWIS HOLE’S HUMAN ANATOMY AND PHYSIOLOGY

LEVELS OF ORGANIZATION Ø TISSUES § 4 TYPES EPITHELIUM, CONNECTIVE TISSUE, MUSCLE & NERVOUS TISSUE Ø ORGANS Ø SYSTEMS

ORGAN SYSTEMS & THEIR FUNCTIONS 1. 2. 3. 4. 5. CARDIOVASCULAR SYSTEM RESPIRATORY SYSTEM DIGESTIVE SYSTEM RENAL SYSTEM REPRODUCTIVE SYSTEM MUSCULOSKELETAL SYSTEM 7. ENDOCRINE SYSTEM 8. NERVOUS SYSTEM 9. IMMUNE SYSTEM 6.

HOMEOSTASIS WALTER CANNON (1871 -1945) HOMEOSTASIS: THE RELATIVELY CONSTANT STATE OF THE COMPOSITION OF THE INTERNAL ENVIRONMENT, ACHIEVED THROUGH HIGHLY COORDINATED PROCESSES. 1926

HOMEOSTASIS CLAUDE BERNARD (1813 -1878) “MILIEU INTERIEUR”, 1887 § INDEPENDENCE OF LIVING BODY FROM SURROUNDING ENVIRONMENT § INTERNAL VS. EXTERNAL ENVIRONMENT

HOMEOSTASIS “IT IS THE FIXITY OF THE INTERNAL ENVIRONMENT THAT IS THE CONDITION OF A FREE AND INDEPENDENT LIFE. ALL THE VITAL MECHANISMS, HOWEVER VARIED THEY MAY BE, HAVE ONLY ONE OBJECT, THAT OF PRESERVING (CONSTANT) THE CONDITIONS OF LIFE IN THE INTERNAL ENVIRONMENT. ” CLAUDE BERNARD

CELL EXTRACELLULAR FLUID, ECF

TOTAL BODY WATER, TBW Ø 60% OF BODY WEIGHT Ø 40% IN INTRACELLULAR FLUID COMPARTMENT (ICF) Ø 20% IN EXTRACELLULAR FLUID COMPARTMENT (ECF) PLASMA, 4% § INTERSTITIAL FLUID, 16% §

INTRACELLULAR FLUID, ICF 40%TBW EXTRACELLULAR FLUID, ECF 20% TBW BLOOD/PLASMA 4% 40% INTERSTITIAL FLUID, 16%

COMPOSITION OF ECF & ICF ECF ICF Na+ 142 m. Eq/L 10 m. Eq/L K+ 4 m. Eq/L 140 m. Eq/L Cl- 103 m. Eq/L 4 m. Eq/L Protein 2 g/dl 16 g/dl Glucose 90 mg/dl - 290 m. Osm/L Osmolality

EXTERNAL & INTERNAL ENVIRONMENT VANDER, SHERMAN, LUCIANO’S HUMAN PHYSIOLOGY, 9 TH ED

HOMEOSTASTIC REGULATION 1. 2. 3. 4. 5. CONCENTRATION OF O 2 & CO 2 PH OF INTERNAL ENVIRONMENT, 7. 4 CONCENTRATION OF NUTRIENTS AND WASTE PRODUCTS CONCENTRATION OF SALT AND OTHER ELECTROLYTES VOLUME AND PRESSURE OF THE ECF

HOMEOSTATIC CONTROL SYSTEMS DISTURBANCE SETPOINT FEEDBACK CONTROLLER + - CONTROLLED VARIABLE EFFECTOR CLOSED LOOP SENSOR RHOADES RA & TANNER GA. MEDICAL PHYSIOLOGY +

CONTROL SYSTEMS Ø NEGATIVE FEEDBACK A DISTURBANCE ELICITS A RESPONSE THAT RESULTS IN AN EFFECT THAT IS OPPOSITE THAT OF THE CHANGE § EG. THERMOSTAT §

CONTROL SYSTEMS EXAMPLE: BODY TEMPERATURE NORMAL, 37 OC W/O, 20 OC, ROOM TEMPERATURE WITH 36. 5 OC

ROOM TEMPERATURE HEAT LOSS FROM BODY TEMPERATURE CONSTRICTION OF SKIN BLOOD VESSELS CURLING UP HEAT LOSS FROM BODY SHIVERING HEAT PRODUCTION RETURN OF BODY TEMPERATURE TOWARD ORIGINAL VALUE

CONTROL SYSTEMS “SET POINT” OR BASELINE RESETTING OF “SET POINT” IN RESPONSE

VANDER, SHERMAN, LUCIANO’S HUMAN PHYSIOLOGY, 6 TH ED

NORMAL RANGE OF VALUES OXYGEN CARBON DIOXIDE Na K GLUCOSE BODY TEMPERATURE p. H 95 -100 mm Hg 35 -45 mm Hg 138 -146 mmol/L 3. 8 -5. 0 mmol/L 75 -95 mg/Dl 36. 5 -37. 5 o. C 7. 35 -7. 45

CONTROL SYSTEMS NORMAL RANGE OF VALUES WITHIN NARROW LIMITS EG. BODY TEMPERATURE, 36. 5 -37. 5 OC APPROXIMATE NONLETHAL LIMITS MAXIMUM LIMITS WITHOUT CAUSING DEATH FOR SHORT PERIODS OF TIME EG. IN CARDIAC ARREST, THERAPEUTIC HYPOTHERMIA, 33 -36 OC

CONTROL SYSTEMS HOW EFFICIENT IS THE CONTROL SYSTEM IN KEEPING THE CONDITION CONSTANT? Ø “GAIN” GAIN = CORRECTION ERROR REF: GUYTON & HALL, MEDICAL PHYSIOLOGY, 11 TH ED

CONTROL SYSTEMS EXAMPLE: BODY TEMPERATURE NORMAL, 37 OC W/O, WITH 20 OC 36. 5 OC GAIN = CORRECTION ERROR (NEW VALUE - STIMULUS) (NEW VALUE - NORMAL) REF: GUYTON & HALL, MEDICAL PHYSIOLOGY

CONTROL SYSTEMS “GAIN” EXAMPLE: BODY TEMPERATURE GAIN = CORRECTION ERROR +16. 5 -0. 5 - 33. 0 REF: GUYTON & HALL, MEDICAL PHYSIOLOGY (36. 5 -20) (36. 5 -37)

CONTROL SYSTEMS “GAIN” EXAMPLE: BLOOD PRESSURE NORMAL, 100 MMHG W/O, 175 WITH 125 REF: GUYTON & HALL, MEDICAL PHYSIOLOGY

CONTROL SYSTEMS EXAMPLE: BLOOD PRESSURE, 100 MM HG DUE TO EXERCISE, 175 MM HG WITH REGULATION, 125 MM HG GAIN = CORRECTION ERROR = (125 -175) (125 -100) GAIN = -2 REF: GUYTON & HALL, MEDICAL PHYSIOLOGY = -50 +25

CONTROL SYSTEMS Ø POSITIVE FEEDBACK A STIMULUS ELICITS A RESPONSE THAT FURTHER INCREASES OR AMPLIFIES THE EFFECT OF THE INITIATING STIMULUS

HOMEOSTATIC CONTROL SYSTEMS DISTURBANCE SETPOINT FEEDBACK CONTROLLER + EFFECTOR CLOSED LOOP SENSOR RHOADES RA & TANNER GA. MEDICAL PHYSIOLOGY CONTROLLED VARIABLE

CONTROL SYSTEMS POSITIVE FEEDBACK PHYSIOLOGIC USEFULNESS: § BLOOD CLOTTING § PARTURITION (AT BIRTH)

BLOOD CLOTTING HTTP: //WWW. BIOLOGY. BUFFALO. EDU/COURSES/BIO 130/MEDLER/LECTURE 1. HTML

IN PARTURITION INCREASED STRETCH OF CERVIX + + + UTERINE CONTRACTIONS + PROSTAGLANDIN SECRETION BY UTERUS +

CONTROL SYSTEMS POSITIVE FEEDBACK VICIOUS CYCLE DEATH

HEMORRHAGIC SHOCK FLOW = PRESSURE X VOLUME DECREASED BLOOD PRESSURE DECREASED CORONARY BLOOD FLOW HEART PUMP FAILURE DEATH

CONTROL SYSTEMS Ø FEEDFORWARD REGULATION § CORRECTIVE RESPONSE PRIOR TO ONSET OF CHANGE ON SET POINT VALUES EG. INCREASED RESPIRATION & HEART RATE BEFORE ACTIVITY IN COMPETITIVE SPORTS § LEARNED/ACQUIRED

ACCLIMATIZATION VS. ADAPTATION (CHANGES IN MORPHOLOGY/ANATOMY)

CHARACTERISTICS OF HOMEOSTATIC CONTROL SYSTEMS SUMMARY § NEGATIVE FEEDBACK SYSTEMS CAUSE RESPONSE BACK TOWARD INITIAL VALUE § CORRECTION WITHIN NARROW RANGE OF NORMAL VALUES

CHARACTERISTICS OF HOMEOSTATIC CONTROL SYSTEMS SUMMARY § SET POINTS OF SOME VARIABLES CAN BE RESET § NOT ALL VARIABLES CAN BE MAINTAINED RELATIVELY CONSTANT

CHARACTERISTICS OF HOMEOSTATIC CONTROL SYSTEMS SUMMARY § BALANCING OF INPUTS AND OUTPUTS • SIMULTANEOUS ACTIVATION OF COUNTER-REGULATORY MECH’MS EG. BLOOD GLUCOSE LEVEL BY INSULIN/GLUCAGON § REDUNDANCY OF CONTROL MECHANISMS FOR VITAL PROCESSES EG. BLOOD GLUCOSE ELEVATED BY GLUCAGON, EPINEPHRINE, GLUCOCORTICOIDS

HOMEOSTASIS DISADVANTAGES OF FEEDBACK CONTROL SYSTEMS SPEED: ACTIVATED BY EFFECT OF STIMULUS § STABILITY: OSCILLATION § ERROR: RESETTING OF BASELINE VALUES §

CONTROL SYSTEMS Ø FEEDFORWARD REGULATION CORRECTIVE RESPONSE PRIOR TO ONSET OF CHANGE ON SET POINT VALUES § LEARNED/ACQUIRED EX: SKILLED MOTOR MOVEMENTS §

CONTROL SYSTEMS Ø ADAPTATIVE CONTROL INVOLVES ANATOMIC CHANGES & PHYSIOLOGIC ADAPTATION MECHANISMS § EVOLVES OVER A PERIOD OF TIME § MORE PERMANENT CHANGES EX: ADAPTATION TO HIGH ALTITUDE §

REFERENCES HOMEOSTASIS Ø GUYTON & HALL. TEXTBOOK OF MEDICAL PHYSIOLOGY, 13 TH ED, CHAP 1 Ø VANDER, LUCIANO & SHERMAN. HUMAN PHYSIOLOGY, 6 TH ED , CHAP 1