Physiology Flashcards
A) Functions of kidney:
- Regulation of water & electrolytes balance
- Regulation of arterial blood pressure (short term: RAAS & long term: Na– H2O excretion)
- Regulation of acid base balance (elimination of acids + regulation of buffer stores)
- Excretion of waste (urea & creatinine) and foreign chemicals (drugs & food additives)
- Endocrine function (erythropoietin → RBCs, activation of vitamin D3, renin secretion)
- Paracrine function (PGs & BK → regulation of RBF)
- Gluconeogenesis
Mechanisms of RBF Autoregulation When BP ↑
Myogenic mechanism:
↑ BP –> stretch of vascular wall —> open stretch gated Ca++ channels —> Ca++influx —> contraction of smooth muscles of afferent arterioles
Tubuologlomerular feedback:
↑ BP —>↑ RBF & GFR —>↑reabsorption of Na & Cl —> ↑ delivery of solutes into macula densa —>macula secretes adenosine –> acts on receptors —> VC of afferent
Mechanism of RBF autoregulation for when BP↓
Myogenic:
↓ BP–> Relaxation of smooth muscles of afferent arterioles
Tubuloglomerular feedback:
↓ BP—> ↓ RBF & GFR—->
↓reabsorption of Na & Cl—-> ↓ delivery of solutes into macula densa —> macula densa: VD of afferent & VC of efferent
Functions of mesangial cells
- Support glomerular capillaries by mesangial matrix.
- Mesangial cells contract —> ↓ filtration surface area.
- Phagocytose immune complex & secretes cytokines.
- Removes debris and aggregated proteins from glomerular membrane.
- Have receptors for vasoactive substances.
Factors affecting GFR
Look at booklet
Give the Na reabsorption in the proximal tubule
65% of filtered Na is reabsorbed in PCT
First half of PCT: Co transport with AA, glucose, phosphate and sulfate, counter transport Na-H counter transporter
Late half of PCT: Na is reabsorbed with Cl passively
Give the Na reabsorption in the Loop of henle
Thin descending limb: Only water reabsorption, No na transporter
Thin ascending limb: No water reabsorption, Na is reabsorbed with Cl passively
Thick ascending limb: 25% of filtered Na is reabsorbed by Co transporter that carries Na, K and Cl. Most K refluxes back into lumen via K channels
Give the Na reabsorption in Distal tubule
Early distal tubule: Na is reabsorbed with Cl by NaCl cotransported
Late distal tubule & collecting duct: Less than 10% of filtered Na is reabsorbed prinicpal cells in exchange with K under aldosterone control.
passive diffusion of Na and K in into principal cells
Regulation of Na excretion
- GFR (glomerulo-tubular balance)
- ↑GFR —>↑ Na and water reabsorption.
- Mechanism: renal tubules reabsorb constant percentage of Na rather than constant amount.
- Importance:
o Prevent overloading of DCT when ↑GFR
o Prevent inappropriate loss of Na or water in - Rate of flow: slow rate —> ↑ Na reabsorption
- ABP.
- Pressure diuresis & natriuresis: ↑ GFR —> ↑ Na & water excretion.
- Mechanism: ↑ ABP —> ↓ Angiotensin II —> ↑ HP in peritubular capillary —-> ↑ HP in renal interstitial fluid —> enhance back leak of Na into tubular lumen –>↓ Na reabsorption & ↑ excretion.
Give the hormonal control for increase of Na reabsorption
Aldosterone: ↑ number of Na+ – K+ ATPase pump in basolateral border.
Glucocorticoids: weak mineralocorticoid activity
Angiotensin II: activate aldosterone secretion, Act directly on PCT stimulate Na —- K ATPase pump
Sex hormone: estrogen
Sympathetic stimulation
- VC of afferent. —> ↓ GFR
- Activate renin —> ↑ RAAS
- Increase Na reabsorption by PCT & thick ascending limb of loop of Henle.
Hormones that decrease Na reabsorption
ANP: increase NaCl excretion. Relaxation of mesangial cells, VD of afferent & VC of Efferent –> increase GFT —> increase Na filtration & reabsorption
PGE2: inhibit Na–K ATPase & Na channels
Endothelin: increase PGE2
Give an account on the obligatory water reabsorption
Proximal tubule: 65% of water is reabsorbed
in proximal tubule by osmosis. Movement of water is facilitated by insertion of aquaporin 1 channels
Loop of Henle:
in descending limb: highly permeable to water by osmosis due to gradual increase in medullary ISF
Early distal tubule & collecting duct: impermeable to water continued dilution of tubular fluid
Give an account on the facultative water reabsorption
In late distal tubule & cortical collecting duct:
↑ADH —-> ↑ number of aquaporin 2 channels —> 8% of filtered water is reabsorbed by osmosis into the interstitium of the cortex.
In medullary duct: 4.7% of filtered water is reabsorbed into medullary hypertonic interstitium —> concentrated urine
Give an account on the mechanism producing hyperosmotic renal medullary interstitium
Countercurrent multiplier system (function of juxtamedullary nephrons of loop of Henle)
Ascending limb:
Thick segment: active reabsorption of solute
Thin segment: passive reabsorption of NaCl
Descending limb: high permeable to water and less permeable to solutes. Water diffuses from descending limb to medullary interstitium by osmosis
Give an account on the mechanism producing hyperosmotic renal medullary interstitium
Countercurrent exchanger system of vasa recta
Descending limb of vasa recta:
Solutes diffuse from medullary ISF into blood along concentration gradient. Water diffuses from blood to ISF
Ascending limb of vasa recta: Solutes diffuse back into medullary ISF along concentration gradient. Water diffuse into vasa recta
Give an account on the mechanism producing hyperosmotic renal medullary interstitium
Contribution of urea
- Urea contributes about 40% of osmolarity of renal medullary ISF.
- At inner medullary CD–> urea moves into medullary ISF —> adding to hyperosmolarity (movement is facilitated by ADH)
- High protein diet –> concentrated urine & vice versa.]
Give an account of the disorders of urine concentration
Diabetes insipidus: polyuria & polydipsia. Polydipsia keeps the patients alive
Syndrome of inappropriate ADH secretion (SIADH)
Water retention –> ECF expansion.
Compare between water diuresis and osmotic diuresis in causes, mechanism, outcome, ADH
Water diuresis: ingestion of large amounts of water. Mechanism: ↑H2O –> ↓ plasma osmolarity –> ↓ ADH —> ↓ facultative reabsorption. Large amount of urine which is very diluted. ADH inhibited
Osmotic diuresis: Large amount of un-reabsorbed solute in tubular fluid.
Mechanism:
a) Un-reabsorbed solutes –> hold water inside tubules –> ↓ obligatory water reabsorption.
b) water retention —>↓ active reabsorption of Na —>↓
Na concentration —> Na retention + ↓ medullary
osmolarity.
Outcome: decrease H2O reabsorption and increase Na
ADH: normal or increased
Give an account on the K handling in renal tubules
K reabsorption: 65% in PCT. In thick ascending limn–> its 25%. In DT and CD it is dependent on K intake
K excretion: By principal cells depending on K intake and aldosterone level. In basolateral border K moves by Na/K ATPase. IN luminal border K moves via electrochemical gradient, K channels, and K–Cl co transporter
Give an account on the glucose reabsorption by renal tubules
All glucose is reabsorbed in early PCT
At luminal border: Glucose transported with NA with SGLT-2. Glucose is carried against concentration gradient
At basolateral border: Glucose is carried along concentration gradient by GLUT-2
Define tubular transport maximum
Tubular transport maximum: maximum amount of actively transported substances that can be reabsorbed per minute
Draw the curve and label each part. Define splay and cause of splay
Splay: is the region of reabsorption curve where reabsorption is reaching saturation but not fully saturated
Heterogeneity of the nephrons
Define Glycosuria and give its causes
Presence of glucose in urine in large amount
Caused by DM and congenital defect in glucose transport
Give the secretion of hydrogen & reabsorption of bicarbonate
Reabsorption of bicarbonate: HCO3- is reabsorbed mainly in PCT (85%), thick ascending loop of Henle (10%) & CD (4.8%). CO2 from blood combines with H2O which from a buffer system
Secretion of hydrogen: H is secreted in all parts of renal tubule except of loop on Henle. In PCT, thick parts of loop on Henle & early DCT–>2ry active transport Na —H counter transport.
Mentions the importance of hydrogen buffering
H secretion occurs as long as pH is > 4.5. IF H not buffered–> limiting pH is reached rapidly–> H secretion stops
Factors affecting H secretion
- aldosterone: ↑ H & K secretion
- Intracellular PCO2: high PCO2 —> ↑ H secretion
- intracellular K: ↑K intracellularly —> ↓ H secretion & vice versa
Mention the pH, reason for, causes and compensation respiratory acidosis.
less than 7.4
↑ PCO2
RC depression, air way obstruction, respiratory muscle
Renal: ↑ PCO2—> formation of H & HCO3 from CO2 in tubular cells. H is secreted to tubular fluid & HCO3 is diffuse back to plasma
Mention the pH, reason for, causes and compensation in respiratory alkalosis
Greater than 7.4
↓ PCO2
High altitudes, fever, hyperventilation
↓ HCO3- Reabsorption + ↓ HCO3- & H+ formation due to ↓CO2
Mention the pH, reason for, causes and compensation in metabolic acidosis
Less than 7.4
↓ HCO3-
Increase protein intake, severe diarrhea
Renal: ↑ HCO3- generation
Mention the pH, reason for, causes and compensation in metabolic alkalosis
Greater than 7.4
↑ HCO3-
Vomiting
Renal: ↓ HCO3- Reabsorption & ↑excretion
Mention the micturition reflex
§ Stimulus: volume of urine in bladder à 300 – 400 ml
§ Receptors: stretch receptors in bladder wall & posterior urethra
§ Afferent: pelvic parasympathetic
§ Efferent: S2 & S3
§ Effector & response: detrusor muscle contraction & internal urethral sphincter relaxation.
Give an account on higher center control and give its function
Facilitatory (2P): pontine & posterior hypothalamus.
Inhibitory: mid-brain
Faciliatory & inhibitory: cortical micturition center
in superior frontal gyrus.
Functions:
1) Keep micturition reflex partly inhibited except
in desired micturition.
2) Prevent micturition even it occurs –>
contraction of external sphincter.
3) When it is time to urinate–> facilitatory centers
facilitate micturition reflex & inhibit external
sphincter.
Give an account on the enteric nervous system
2 neural plexuses: myenteric plexus in control of peristalic activity while Submucosal plexus controls exocrine & endocrine secretion
These neurons secrete: NO, ach, serotonin, GABA
Explain the site of release, stimuli and actions of gastrin
G cells
Distention of stomach, vagal stimulation, chemical stimuli like soup
Simulate gastric motility, increase acid and pepsin secretion
Explain the site of release, stimuli and actions of Cholecystokinin-Pancreozymin.
APUD cells in upper intestine
Presence of peptide, AA and fat in small intestine
Stimulates pancreatic acini, inhibit gastric motility, enhance intestinal motility, stimulate insulin secretion
Explain the site of release, stimuli and actions of secretin
APUD cells in upper intestine
decrease pH in intestinal fluid < 4.5
Stimulates pancreatic duct, decrease gastric acid secretion, augment action of CCK
Describe Pharyngeal stage of swallowing
Stimulus: bolus of food in pharynx
Receptor: pharyngeal opening
Center: in medulla
Response: rapid peristaltic wave in superior then middle then inferior pharyngeal muscles and upper pharyngoesophageal sphincter relaxes
Give the stimuli of secretion and actions of gastric inhibitory peptide and Vasoactive intestinal peptide
GIP:
Stimuli of secretion: presence of fat and glucose in duodenum
Actions: decrease HCl secretion and stimulate insulin secretion
VIP:
Stimuli of secretion: digestive products in intestine.
Actions: VC of intestinal vessels, inhibit gastric secretion, relaxation of GIT smooth muscles
Give the site of release, stimuli secretion, actions of Motilin and Somatostatin (GHIH)
Motilin
Stimuli of secretion: digestive products
Actions: Stimulates duodenal motility and contraction of lower esophageal sphincter
Somatostatin (GHIH)
Stimuli of secretion: presence of HCl
Actions: inhibit gastrin, secretin, GIP, VIP. Inhibits gastric acid secretion
Describe involuntary Esophageal stage of swallowing?
- Primary peristaltic wave: continuation of peristaltic wave begins in pharynx, passes all the way from pharynx to stomach in 8 to 10 seconds.
- Secondary peristaltic waves: result from distention of the esophagus by the retained food if primary peristaltic wave fails to move all the food into stomach
Describe function and control of lower esophageal sphincter
Sphincter: remains tonically contracted, in contrast to the mid and upper esophagus
Function: prevent reflux of gastric contents into esophagus (regurgitation)
When peristaltic waves passes down the esophagus –> “receptive relaxation” relaxes LES–> easy food propulsion
Tone of LES under control of Ach, NO & VIP, diet
Give the abnormalities of the tone of LES
Gastroesophageal reflux: decrease resting tone of LES –> reflux of gastric acid content into esophageal —> heartburn and esophagitis
Achalasia: incomplete relaxation of LES–> accumulation of food—> massive dilation of esophagus.
Discuss the regulation of gastric evacuation
- Gastric factors: Distension of the stomach –> increase emptying via
x Nervous reflexes: long vago-vagal reflexes, short local reflexes
x Hormonal: gastrin
- Intestinal factors: decrease emptying
a. Nervous: (Enterogastric Reflex):increase irritation and acidity, decrease emptying
b. Hormonal: presence of fat in duodenum –>releases (CCK, GIP and secretin)
- Consistency of food: Liquid food is evacuated more rapidly > solids
- Reflexes from outside the GIT: Pain—>emptying
Give the causes, center and mechanism of vomiting
Causes of vomiting:
x Reflex:
a. Mechanical stimulation of the posterior part of the tongue.
b. Irritation of the gastric mucosa
c. Irritation or obstruction of the intestine
Central: stimulate vomiting center
A- Drugs: apomorphine
B- Hypoxia and acidosis
C- Motion sickness
- Stomach wall is completely passive:
- Relaxation of the wall of the stomach.
- Relaxation of LES.
- Contraction of pyloric sphincter
- Deep inspiration followed by contraction of abdominal muscles–> increase intra-abdominal pressure —> squeeze gastric contents up through a relaxed LES
Vomiting centers in medulla which is associated with respiratory center
Give an account on defecation spinal reflex?
Stimulus: rectal distention
Afferent: pelvic nerve
Receptors: sensory nerve endings in the rectum
Center: sacral segments of spinal cord
Efferent: reflex back in pelvic nerves
response: contraction of smooth muscle distal colon and relaxation of internal anal sphincter
Describe the mechanism of salivary secretion
First stage: acini secrete 1ry secretion, has ionic composition, 1ry secretion is isotonic
Secondary stage: ducts modify primary secretion, Na is reabsorbed in exchange with K. This decrease Na, Cl in saliva, while increase K, HCO3 in plasma. 2nd secretion is hypotonic
Explain control of salivary secretion
Parasympathetic: center is in superior and inferior salivary nucleus: superior for sublingual and inferior for parotid gland. It causes marked VD which profuse secretion of watery saliva
Secretion of saliva:
Stimulus: taste, tactile stimuli from mouth and upper intestine
Conditioned:
Stimulus: sight, smell, preparation of food
Mechanism of acid secretion
- H2O dissociates into H+ and OH- in the cell.
- H+ is actively secreted to lumen in exchange for K+ by H+/K+ ATPase pump
- CO2 (formed during metabolism or entering by blood and HCO3 is formed
- HCO3- diffuses out of the cell ї to blood in exchange for Cl-
- Cl- is actively transported to the lumen
- H2O passes to the lumen by osmosis.
List Stimuli of HCL secretion & their mechanism of action, functions of HCL
Histamine: acts on H2 receptor increase cAMP
Ach: acts on M3 receptors, increase intracellular Ca
Gastrin: acts directly by increase Ca intracellular
Describe the 3 phases of gastric secretion
- Cephalic stimulatory phase: (Nervous)—> 1/3 of gastric secretion
x Both conditioned and unconditioned reflexes –> stimulate vagus—> increase gastric secretion by:
a. Acetylcholine–>acts directly on parietal cells.
b. Gastrin-releasing peptide–> increase gastrin secretion. - Gastric stimulatory phase: (Nervous and Hormonal)–>2/3 gastric secretion): via
a. Long vago-vagal reflexes
b. Local enteric reflexes (submucous plexus)
c. Gastrin secretion. - Intestinal inhibitory phase: (Nervous and Hormonal)–> decrease gastric secretion by:
A. Enterogastric reflex.
B. Hormones inhibit gastric secretion, such as GIF, VIP, CCK and secretin.
Mention the control of peristalsis of SI
Nervous regulation by gastroenteric reflex: initiated by distention of stomach –> conducted via myenteric plexus from stomach along SI
Hormonal regulation: gastrin, CCK, insulin, motilin and serotonin
list Mechanisms of inhibition of gastric secretion?
- decrease pH< 2 in pyloric region & duodenum–> decrease gastrin
- Enterogastric reflex
- Presence of fat and hypertonic sugars in duodenum–> increase GIP, CCK, secretin and VIP.
- Emotional depression and fear, via impulses from cerebral cortex–> inhibit dorsal vagal nucleus.
- Somatostatin (paracrine).
Describe the mucosal barrier? formed of
- Insoluble mucus (glycoproteins = mucins): secreted by surface mucous cells —> flexible coating gel
- HCI secreted by parietal cells in gastric glands crosses this barrier in finger like channels,
- Integrity of the membrane of mucosal cells:
o Membrane is impermeable to H+
o Active transport —> pumping H+ from mucosal cell into lumen, and Na+ from the cells into ISF. - Prostaglandins
o Strengthen and augment gastric mucosal barrier
o inhibit acid secretion
Discuss role of liver in controlling appetite?
јsugar levels їј FGF21 secretion from liverї signals to PVN in hypothalamus ї љ,K
ŝŶƚĂŬĞїљsweet-seeking behavior and meal size.
- FGF21: also ј insulin sensitivity & modulation of hepatic fatty acid oxidation and ketogenesis
Discuss regulation of pancreatic secretion
During cephalic & gastric phases of gastric secretion —> increase parasympathetic vagal discharge—> release acetylcholine—> activating phospholipase C in pancreatic acinar cells —> secretion of small amount of pancreatic juice rich in enzymes.
Discuss the hormonal function and immunological functions of liver
Hormonal functions:
Secretes IGF-1 which is involved in growth as well as angiotensinogen.
Immunity: liver is rich in cells of immune system like NK cells and Kupffer cells which secrete cytokines and activates immune system.
